EDITORIAL ESPANOL:

====================

Hola amigos DERMAGICOS, en la edición de hoy, una revisión sobre el tema NECROBIOSIS LIPOIDICA DIABETICORUM, bastante difícil de tratar por cierto. Estas 34 referencias bibliográficas nos actualizan sobre esta compleja patología, manifestación clínica de la diabetes. Hay una NECROBIOSIS LIPOIDICA NO DIABETICORUM, la cual sera motivo de otra revisión. 

A partir de esta edición en lo posible mandare imagenes ilustrativas del tema. En esta oportunidad en el attach una lamina con 3 fotos de necrobiosis lipoidica diabeticorum. 

Dr. Oscar Mario T, encontré varios artículos interesantes sobre la DERMATOSCOPIA, motivo de la próxima edición, saludos Argentina. 

Hasta la próxima edición: LA DERMATOSCOPIA. 

Saludos a TODOS,,, 

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

===================

Hello DERMAGICS friends, in today's edition, a revision on the topic NECROBIOSIS LIPOIDICA DIABETICORUM, quite difficult of trying by the way. These 34 bibliographical references modernize us on this complex pathology, clinical manifestation of the diabetes. There is a NECROBIOSIS LIPOIDICA NON DIABETICORUM, which will be reason of another revision. 

Starting from this edition as much as possible I will send illustrative images of the topic. In this opportunity in the attach a sheet with 3 pictures of necrobiosis lipoidica diabeticorum. 

Dr. Oscar Mario T, I found several interesting articles on the DERMATOSCOPY, reason of the next edition, greetings Argentina. 

Until the next edition: THE DERMATOSCOPY 

Greetings to ALL, 

Dr. José Lapenta,

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DERMAGIC/EXPRESS(40)

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NECROBIOSIS LIPOIDICA DIABETICORUM

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1.) Necrobiosis lipoidica diabeticorum: a clinicopathologic study. 

2.) Ulcerated necrobiosis lipoidica diabeticorum in a patient with a

history of generalized granuloma annulare. 

3.) Necrobiosis lipoidica diabeticorum with cholesterol clefts in the

differential diagnosis of necrobiotic xanthogranuloma. 

4.) Necrobiosis lipoidica diabeticorum: association with background

retinopathy, smoking, and proteinuria. A case controlled study. 

5.) Necrobiosis lipoidica diabeticorum: platelet survival and response to

platelet inhibitors. 

6.) [Necrobiosis lipoidica diabeticorum in children. Description of a case] 

7.) Treatment of necrobiosis lipoidica diabeticorum by hyperbaric oxygen. 

8.) Perforating elastosis in necrobiosis lipoidica diabeticorum. 

9.) Necrobiosis lipoidica diabeticorum in children and adolescents: a clue

for underlying renal and retinal disease. 

10.) The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. 

11.) A new histopathologic feature of necrobiosis lipoidica diabeticorum:

lymphoid nodules. 

12.) Koebner's phenomenon and necrobiosis lipoidica diabeticorum. 

13.) Expression of interstitial collagenase, 92-kDa gelatinase, and tissue

inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis

lipoidica diabeticorum. 

14.) Necrobiosis lipoidica and diabetic control revisited. 

15.) Psoriasis, necrobiosis lipoidica, granuloma annulare, vitiligo and

skin infections in the same diabetic patient. 

16.) Ulcerating necrobiosis lipoidica resolving in response to

cyclosporine-A. 

17.) [Ulcerated necrobiosis lipoidica associated with insulin-dependent

diabetes mellitus. Beneficial effect of corticosteroid therapy by oral

administration] 

18.) Treatment with benzoyl peroxide of ulcers on legs within lesions of

necrobiosis lipoidica diabeticorum.

19.) The surgical treatment of necrobiosis lipoidica diabeticorum.

20.) Necrobiosis lipoidica. An immunofluorescence study.

21.) Ulcerated necrobiosis lipoidica diabeticorum in a patient with a

history of generalized granuloma annulare.

22.) [Necrobiosis lipoidica (diabeticorum) and its association to

Miescher's granulomatosis disciformis chronica et progressiva]

23.) Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline.

24.) Expression of interstitial collagenase, 92-kDa gelatinase, and tissue

inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis

lipoidica diabeticorum.

25.) Granuloma annulare, necrobiosis lipoidica, and diabetic disease. 

26.) Resolution of necrobiosis lipoidica with exclusive clobetasol

propionate treatment.

27.) High dose nicotinamide in the treatment of necrobiosis lipoidica.

28.) Skin blood flow in necrobiosis lipoidica during treatment with

low-dose acetylsalicylic acid.

29.) [Clofazimine--therapeutic alternative in necrobiosis lipoidica and

granuloma anulare]

30.) Treatment of necrobiosis lipoidica with low-dose acetylsalicylic acid.

A randomized double-blind trial.

31.) [Necrobiosis lipoidica in a patient with bronze diabetes]

32.) Serum alpha 2 globulin levels in granuloma annulare and necrobiosis

lipoidica.

33.) Increased natural autoantibody activity to cytoskeleton proteins in

sera from patients with necrobiosis lipoidica, with or without

insulin-dependent diabetes mellitus.

34.) An unusual case of giant dermatofibroma in a patient with diabetes

mellitus and necrobiosis lipoidica.

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1.) Necrobiosis lipoidica diabeticorum: a clinicopathologic study. 

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Author 

Boulton AJ; Cutfield RG; Abouganem D; Angus E; Flynn HW Jr; Skyler JS;

Penneys NS 

Address 

Department of Medicine, University of Miami School of Medicine, FL. 

Source 

J Am Acad Dermatol, 18(3):530-7 1988 Mar 

Abstract 

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. 

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2.) Ulcerated necrobiosis lipoidica diabeticorum in a patient with a

history of generalized granuloma annulare. 

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Author 

Berkson MH; Bondi EE; Margolis DJ 

Address 

Department of Dermatology, Hospital of the University of Pennsylvania,

Philadelphia 19104. 

Source 

Cutis, 53(2):85-6 1994 Feb 

Abstract 

Granuloma annulare and necrobiosis lipoidica diabeticorum have rarely been

reported in the same patient. We describe the unusual case of a woman with

diabetes and a history of generalized granuloma annulare who noted leg

ulcers that clinically represented ulcerated necrobiosis lipoidica

diabeticorum and had histologic features of necrobiosis lipoidica

diabeticorum and granuloma annulare. Her condition responded to treatment

with antiplatelet agents. 

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3.) Necrobiosis lipoidica diabeticorum with cholesterol clefts in the

differential diagnosis of necrobiotic xanthogranuloma. 

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Author 

Gibson LE; Reizner GT; Winkelmann RK 

Address 

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

Source 

J Cutan Pathol, 15(1):18-21 1988 Feb 

Abstract 

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. 

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4.) Necrobiosis lipoidica diabeticorum: association with background

retinopathy, smoking, and proteinuria. A case controlled study. 

========================================================================

Author 

Kelly WF; Nicholas J; Adams J; Mahmood R 

Address 

Diabetes Care Centre, Middlesborough General Hospital, UK. 

Source 

Diabet Med, 10(8):725-8 1993 Oct 

Abstract 

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. 

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5.) Necrobiosis lipoidica diabeticorum: platelet survival and response to

platelet inhibitors. 

========================================================================

Author 

Quimby SR; Muller SA; Schroeter AL; Fuster V; Kazmier FJ 

Address 

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

Source 

Cutis, 43(3):213-6 1989 Mar 

Abstract 

Results of an open trial of platelet inhibitor treatment for necrobiosis

lipoidica diabeticorum suggest the possible importance of abnormal platelet

function in this disease. In ten female patients with necrobiosis lipoidica

diabeticorum (six who were diabetic and four who were not) platelet

survival times were measured before and after treatment with aspirin and

dipyridamole. Pretreatment platelet survival time was considerably

shortened in 50 percent of the diabetic and nondiabetic patients.

Platelet-inhibitor treatment prolonged platelet survival time toward normal

in most of these patients. The clinical response to treatment varied from

healing to no noticeable effect. 

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6.) [Necrobiosis lipoidica diabeticorum in children. Description of a case] 

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Author 

Zaccone C; Vignoli GP; Vignati G; Borroni G 

Address 

Dipartimento di Patologia Umana ed Ereditaria, Universit`a di Pavia. 

Source 

G Ital Dermatol Venereol, 125(5):225-8 1990 May 

Abstract 

A case of necrobiosis lipoidica diabeticorum (NLD) in a 12-year-old male

patient is described. Diabetes mellitus (DM) was diagnosed at the age of

1.5 years. The onset of the first NLD lesion had been previously observed

at the age of 7, on the back of the left foot. Three new lesions appeared

at the age of 8, one on the left leg, the others on the thighs. At the age

of 12, four infiltrated, reddish patches, with slight central atrophy were

evident on his lower extremities. Histopathological features showed foci of

collagen degeneration with sclerosis, surrounded by a chronic, mainly

perivascular, granulomatous infiltrate, made up of lymphocytes and

histiocytes. The patient is now 19-year old, with no eye or kidney failure,

owing to a constant metabolic control of DM. A constant follow-up of the

patient demonstrated a self-resolution of NLD plaques, with no evidence of

further lesions. 

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7.) Treatment of necrobiosis lipoidica diabeticorum by hyperbaric oxygen. 

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Author 

Weisz G; Ramon Y; Waisman D; Melamed Y 

Address 

Israeli Naval Hyperbaric Institute, Haifa. 

Source 

Acta Derm Venereol, 73(6):447-8 1993 Dec 

Abstract 

Necrobiosis lipoidica diabeticorum is a chronic cutaneous complication of

diabetes mellitus with microangiopathy as an important pathophysiologic

factor. Because of the known success of hyperbaric oxygen in the treatment

of chronic non-healing wounds, we used this mode of therapy to treat a

diabetic patient with ulcerated necrobiosis lipoidica of 7 years' duration,

refractory to medical and surgical treatment. The patient received daily

sessions of hyperbaric oxygen therapy. There was considerable improvement

during the course of the treatment, with complete closure of all the

ulcerations after 98 sessions. The success of this treatment emphasizes the

role of hypoxia in the pathogenesis of the lesion. This simple and safe

treatment method may be a good solution for patients with chronic

nonhealing necrobiosis lipoidica which fails to respond to other

therapeutic approaches. 

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8.) Perforating elastosis in necrobiosis lipoidica diabeticorum. 

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Author 

McDonald L; Zanolli MD; Boyd AS 

Address 

Department of Medicine, Vanderbilt University Medical Center, Nashville,

Tennessee 37232-5229, USA. 

Source 

Cutis, 57(5):336-8 1996 May 

Abstract 

A 58-year-old diabetic woman with necrobiosis lipoidica diabeticorum

demonstrated lesions with raised, prominent borders. These areas were found

on biopsy to have transepidermal elimination of elastic fibers. We present

this case as a unique finding and review the characteristics and possible

mechanisms of transepidermal elimination. 

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9.) Necrobiosis lipoidica diabeticorum in children and adolescents: a clue

for underlying renal and retinal disease. 

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Author 

Verrotti A; Chiarelli F; Amerio P; Morgese G 

Address 

Department of Pediatrics, University of Chieti, Italy. 

Source 

Pediatr Dermatol, 12(3):220-3 1995 Sep 

Abstract 

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. 

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10.) The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. 

========================================================================

Author 

Quimby SR; Muller SA; Schroeter AL 

Address 

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

Source 

Arch Dermatol, 124(9):1364-71 1988 Sep 

Abstract 

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. Vasculopathy 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. 

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11.) A new histopathologic feature of necrobiosis lipoidica diabeticorum:

lymphoid nodules. 

========================================================================

Author 

Alegre VA; Winkelmann RK 

Address 

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

Source 

J Cutan Pathol, 15(2):75-7 1988 Apr 

Abstract 

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. 

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12.) Koebner's phenomenon and necrobiosis lipoidica diabeticorum. 

========================================================================

Author 

Llajam MA 

Address 

Department of Medicine, College of Medicine, King Saud University, Riyadh,

Saudi Arabia. 

Source 

Br J Clin Pract, 44(12):765 1990 Dec 

Abstract 

In 1877, Dr Heinrich Koebner inflicted an experimental trauma on the

uninvolved skin of a psoriatic patient. This resulted in the appearance of

a typical psoriatic lesion at the site of trauma. This reaction, known as

Koebner's phenomenon (KP), has subsequently been associated with several

skin diseases. However, it has not been associated previously with

necrobiosis lipoidica diabeticorum (NBL), a rare skin manifestation of

diabetes mellitus. This report presents the unusual finding of NBL

associated with KP in a patient with diabetes mellitus. 

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13.) Expression of interstitial collagenase, 92-kDa gelatinase, and tissue

inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis

lipoidica diabeticorum. 

========================================================================

Author 

Saarialho-Kere UK; Chang ES; Welgus HG; Parks WC 

Address 

Division of Dermatology, Jewish Hospital, Washington University Medical

Center, St. Louis, MO 63110. 

Source 

J Invest Dermatol, 100(3):335-42 1993 Mar 

Abstract 

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. 

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14.) Necrobiosis lipoidica and diabetic control revisited. 

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Author 

Cohen O; Yaniv R; Karasik A; Trau H 

Address 

Institute of Endocrinology, C. Sheba Medical Center, Tel Hashomer and

Sackler School of Medicine, Tel-Aviv University, Israel. 

Source 

Med Hypotheses, 46(4):348-50 1996 Apr 

Abstract 

Necrobiosis lipoidica diabeticorum is a rare skin disorder, usually

considered a marker for diabetes mellitus. More than half of the patients

with necrobiosis lipoidica diabeticorum have diabetes mellitus, but less

than one per cent of diabetes mellitus patients have necrobiosis lipoidica

diabeticorum. In the diabetes and dermatology literature, we find the

position that there is no effect of glucose control on either the

appearance of necrobiosis lipoidica diabeticorum or the clinical course of

the lesion. We base our challenge to this position on a critical review of

the original data. And conclude on the contrary, that necrobiosis lipoidica

diabeticorum is usually associated with poor glucose control and that

tighter glucose control, as currently practised, might improve or prevent

the disorder. 

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15.) Psoriasis, necrobiosis lipoidica, granuloma annulare, vitiligo and

skin infections in the same diabetic patient. 

========================================================================

Author 

Abraham Z; Lahat N; Kinarty A; Feuerman EJ 

Address 

Department of Dermatology, Reish Policlinic, Haifa, Israel. 

Source 

J Dermatol, 17(7):440-7 1990 Jul 

Abstract 

A diabetic patient is described presenting psoriasis, necrobiosis lipoidica

diabeticorum, granuloma annulare, and vitiligo and with a history of

recurrent erysipelas and mycotic infections. Scrupulous physical

examination excluded further systemic or cutaneous involvement. The

immunological workup revealed both phenotypic and functional defects in

cellular immunity. 

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16.) Ulcerating necrobiosis lipoidica resolving in response to

cyclosporine-A. 

========================================================================

Author 

Smith K 

Source 

Dermatol Online J, 3(1):2 1997 Mar 

Abstract 

Necrobiosis lipoidica often fails to respond adequately to therapy with

topical and intralesional corticosteroids, or to systemic medications like

niacinamide and pentoxifylline (Trental). On the basis of unpublished work

which showed a predominance of T helper cells in lesions of necrobiosis

lipoidica, and recalling the case of a woman whose necrobiosis lipoidica

improved after she was started on cyclosporine for a renal transplant,

systemic cyclosporine was successfully used in the cases of two young women

who had insulin-dependent diabetes and were disfigured by severe,

ulcerating necrobiosis lipoidica on the anterior lower legs. Response to

treatment was monitored with photographs. In both cases the ulcers

resolved, and remained in remission after cyclosporine was stopped. 

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17.) [Ulcerated necrobiosis lipoidica associated with insulin-dependent

diabetes mellitus. Beneficial effect of corticosteroid therapy by oral

administration] 

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Author 

Hocqueloux L; Gautier JF; Lebbe C; Jellal M; Vexiau P; Morel P; Cathelineau G 

Address 

Service d'Endocrinologie, H^opital Saint-Louis, Paris. 

Source 

Presse Med, 25(1):25-7 1996 Jan 6-13 

Abstract 

OBJECTIVES: Necrobiosis lipoidica is a rare degenerative disease of dermal

connective tissue usually observed in young diabetic patients. Several

drugs have been suggested to be useful, but none have been shown to be

effective in all cases. CASE REPORT: A young patient with insulin-dependent

diabetes had a severe invalidating ulcerated necrobiosis lipoidica. Oral

corticosteroids led to a satisfactory regression then stabilization with 6

mg/d prednisone. DISCUSSION: Oral corticosteroids would appear to be

effective treatment and should be validated by controlled studies.

Corticosteroids should only be used in exceptionally severe forms of

ulcerated necrobiosis lipoidica after failure of conventional treatments.

Diabetes would be an indication under strict metabolic control. 

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18.) Treatment with benzoyl peroxide of ulcers on legs within lesions of

necrobiosis lipoidica diabeticorum.

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SO - J Dermatol Surg Oncol 1978 Sep;4(9):701-4

AU - Hanke CW; Bergfeld WF

PT - JOURNAL ARTICLE

AB - A lotion of 20% benzoyl peroxide was applied to ulcers on legs from

necrobiosis lipoidica diabeticorum. The ulcers healed rapidly and

uneventfully, leaving firm, yellow scars. The efficacy and simplicity of

use of topical benzoyl peroxide therapy is discussed.

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19.) The surgical treatment of necrobiosis lipoidica diabeticorum.

======================================================================

SO - Plast Reconstr Surg 1977 Sep;60(3):421-8

AU - Dubin BJ; Kaplan EN

PT - JOURNAL ARTICLE

AB - We review the literature on the surgical treatment of necrobiosis

lipoidica diabeticorum, and we describe 7 cases treated at Stanford

University Medical Center. Experiences with them prompt us to recommend

surgical excision of the lesions down to the deep fascia, ligation of the

associated perforating blood vessels, and the use of split-skin grafts to

cover the defects. There were no recurrences when we did all these things.

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20.) Necrobiosis lipoidica. An immunofluorescence study.

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SO - Arch Dermatol 1977 Dec;113(12):1671-3

AU - Ullman S; Dahl MV

PT - JOURNAL ARTICLE

AB - Biopsy specimens from 12 patients with necrobiosis lipoidica

(diabeticorum) were studied by direct immunofluorescent microscopy. The

immunoglobulin IgM was present in blood vessel walls of involved skin from

six patients, and the third component of complement (C3) was present in the

blood vessel walls of involved skin from seven patients. The immunoglobulin

IgA was similarly observed in two patients. In addition, IgM, C3, or

fibrinogen were observed at the dermal-epidermal junction of involved skin

from seven patients. Necrobiotic areas invariably contained fibrinogen.

These findings suggest that an immunecomplex vasculitis may be involved in

the pathogenesis of necrobiosis lipoidica.

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21.) Ulcerated necrobiosis lipoidica diabeticorum in a patient with a

history of generalized granuloma annulare.

======================================================================

SO - Cutis 1994 Feb;53(2):85-6

AU - Berkson MH; Bondi EE; Margolis DJ

AD - Department of Dermatology, Hospital of the University of

Pennsylvania, Philadelphia 19104.

PT - JOURNAL ARTICLE

AB - Granuloma annulare and necrobiosis lipoidica diabeticorum have rarely

been reported in the same patient. We describe the unusual case of a woman

with diabetes and a history of generalized granuloma annulare who noted leg

ulcers that clinically represented ulcerated necrobiosis lipoidica

diabeticorum and had histologic features of necrobiosis lipoidica

diabeticorum and granuloma annulare. Her condition responded to treatment

with antiplatelet agents.

======================================================================

22.) [Necrobiosis lipoidica (diabeticorum) and its association to

Miescher's granulomatosis disciformis chronica et progressiva]

[Uber die Necrobiosis lipoidica (diabeticorum) sowie zur Frage der

Zugehorigkeit der Granulomatosis disciformis chronica et progressiva

Miescher.]

======================================================================

SO - Hautarzt 1983 Jul;34(7):322-5

AU - Gotz H

PT - JOURNAL ARTICLE; REVIEW (14 references)

AB - Morphologically, clinically and histologically the picture of

necrobiosis lipoidica with and without diabetes represents an entity. In

our opinion, granulomatosis disciformis chronica et progressiva Miescher

reflects a specific reaction type of necrobiosis lipoidica being influenced

by genetic factors. Its histological appearance is characterised by

tuberculoid or sarcoid-like structures, in which the damage of the collagen

as defined by necrobiosis, is variable but never absent. With regard to the

factor of age, the concurrence of necrobiosis lipoidica sine diabete with

granulomatosis disciformis Miescher in the middle of the period of life

also speaks in favour of the similarity of both skin disorders. An injury

seems to represent one of the conditional factors for the outbreak of the

disease. The analysis of the histological slides revealed furthermore that

the damage of the skin is confined to the clinically recognizable lesion.

For its pathogenesis a local disturbance of the metabolism in the skin

seems to be decisive i.e., the disturbance of the carbohydrate metabolism

(shift from the citrate cycle to the pentosephosphate cycle, associated

with the stimulation of fatty acid production). In the abnormal metabolism

of the carbohydrates, the diabetes mellitus must be considered as the most

important factor, however not excluding others as yet still unknown.

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23.) Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline.

======================================================================

SO - Clin Exp Dermatol 1993 Jan;18(1):78-9

AU - Noz KC; Korstanje MJ; Vermeer BJ

AD - Department of Dermatology, Academic Hospital Leiden, The Netherlands.

PT - JOURNAL ARTICLE

AB - 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 acetylsalicylic acid. However, the ulcers healed completely within 8

weeks of administration of 400 mg pentoxifylline twice daily.

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24.) Expression of interstitial collagenase, 92-kDa gelatinase, and tissue

inhibitor of metalloproteinases-1 in granuloma annulare and necrobiosis

lipoidica diabeticorum.

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

AU - Saarialho-Kere UK; Chang ES; Welgus HG; Parks WC

AD - Division of Dermatology, Jewish Hospital, Washington University

Medical Center, St. Louis, MO 63110.

PT - JOURNAL ARTICLE

AB - 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 

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25.) Granuloma annulare, necrobiosis lipoidica, and diabetic disease

======================================================================

[published erratum appears in Int J Dermatol 1990 Mar; 29(2):120]

SO - Int J Dermatol 1988 Oct;27(8):576-9

AU - Binazzi M; Simonetti S; Simonetti V [corrected to Simonetti S]

AD - Department of Dermatology and Venereology, University of Perugia

School of Medicine, Italy.

PT - JOURNAL ARTICLE

AB - One hundred sixteen patients with granuloma annulare and necrobiosis

lipoidica were studied. The relationship of these two disorders with

diabetes mellitus suggests that atypical granuloma annulare could be linked

to necrobiosis lipoidica, toward which it progresses.

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26.) Resolution of necrobiosis lipoidica with exclusive clobetasol

propionate treatment.

SO - J Am Acad Dermatol 1990 May;22(5 Pt 1):855-6

AU - Goette DK

AD - Department of Medicine, Letterman Army Medical Center, Presidio of

San Francisco, CA 94129-6700.

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27.) High dose nicotinamide in the treatment of necrobiosis lipoidica.

======================================================================

SO - Br J Dermatol 1988 May;118(5):693-6

AU - Handfield-Jones S; Jones S; Peachey R

AD - Department of Dermatology, Bristol Royal Infirmary, U.K.

PT - JOURNAL ARTICLE

AB - An open study of high dose nicotinamide in the treatment of 15

patients with necrobiosis lipoidica is reported. Of 13 patients who

remained on treatment for more than 1 month, eight improved. Improvement

took the form of a decrease in pain and soreness, a decrease in erythema

and the healing of ulcers if present, although the skin did not return

completely to normal in any patient. There were no significant

side-effects, particularly with respect to diabetic control, an important

finding as lesions tended to relapse if treatment was stopped.

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28.) Skin blood flow in necrobiosis lipoidica during treatment with

low-dose acetylsalicylic acid.

======================================================================

SO - Acta Derm Venereol 1988;68(4):364-5

AU - Beck HI; Bjerring P

AD - Department of Dermatology and Venerology, Marselisborg Hospital,

Arhus, Denmark.

PT - JOURNAL ARTICLE

AB - Skin blood flow was measured by the laser Doppler technique in

lesional and clinically normal skin of 10 diabetic patients with

necrobiosis lipoidica during and after treatment with 40 mg acetylsalicylic

acid (ASA) daily. The measurements showed that the blood flow during ASA

treatment was significantly decreased in the central lesional skin without

changes in the peripheral part of the lesions and normal skin. In view of

these findings we suggest that low-dose ASA may not be the best treatment

for necrobiosis lipoidica.

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29.) [Clofazimine--therapeutic alternative in necrobiosis lipoidica and

granuloma anulare]

TT - [Clofazimine--therapeutische Alternative bei Necrobiosis lipoidica

und Granuloma anulare.]

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SO - Hautarzt 1989 Feb;40(2):99-103

AU - Mensing H

AD - Universitats-Hautklinik Hamburg, Eppendorf.

MC - English Abstract

PT - JOURNAL ARTICLE

AB - Twenty patients, ten suffering from disseminated granuloma anulare

and ten from necrobiosis lipoidica, were treated with clofazimine 200 mg

p.o. daily. Six patients in each group (60%) responded to this regimen, and

three of the responders in each group achieved complete remission of the

dermatosis. In eight patients (40%) no improvement at all was observed. All

the patients treated had reddening of the skin, but this was reversible

after the end of therapy, as were the other side-effects, i.e. diarrhoea

and dryness of the skin, which were not experienced by all patients.

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30.) Treatment of necrobiosis lipoidica with low-dose acetylsalicylic acid.

A randomized double-blind trial.

======================================================================

SO - Acta Derm Venereol 1985;65(3):230-4

AU - Beck HI; Bjerring P; Rasmussen I; Zachariae H; Stenbjerg S

PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

AB - 16 patients with clinically and histologically verified necrobiosis

lipoidica lesions were treated with either 40 mg acetylsalicylic acid or

placebo daily for 24 weeks in a double-blind controlled study. The lesions

became statistically significantly larger in both groups in spite of

inhibition of the aggregation of the platelets in the acetylsalicylic group.

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31.) [Necrobiosis lipoidica in a patient with bronze diabetes]

TT - [Necrobiosis lipoidica bei einem Patienten mit Bronzediabetes.]

======================================================================

SO - Hautarzt 1984 Aug;35(8):418-20

AU - Graudal C; Andersen AR; Lange K; Povlsen CO

PT - JOURNAL ARTICLE

AB - A case of necrobiosis lipoidica in a patient with idiopathic

hemochromatosis and diabetes mellitus is presented. Histologic examination

revealed excessive amounts of iron pigment in macrophages in the corium of

the necrobiotic skin. There were no iron deposits in the normal skin.

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32.) Serum alpha 2 globulin levels in granuloma annulare and necrobiosis

lipoidica.

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SO - Br J Dermatol 1981 Nov;105(5):557-62

AU - Majewski BB; Barter S; Rhodes EL

PT - JOURNAL ARTICLE

AB - 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.

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33.) Increased natural autoantibody activity to cytoskeleton proteins in

sera from patients with necrobiosis lipoidica, with or without

insulin-dependent diabetes mellitus.

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AU - AUTHOR(S): Haralambous-S; Blackwell-C; Mappouras-DG; Weir-DM;

Kemmett-D; Lymberi-P

AD - ADDRESS OF AUTHOR: Department of Immunology, Hellenic Pasteur

Institute, Athens, Greece.

SO - SOURCE (BIBLIOGRAPHIC CITATION): Autoimmunity. 1995; 20(4): 267-75

AB - ABSTRACT: Necrobiosis lipoidica (NL), a skin disease, is associated

with insulin-dependent diabetes mellitus (IDDM). Natural autoantibody (NAb)

activity in sera from 16 patients suffering from NL, with or without IDDM,

was compared to that in sera from 41 patients with IDDM and 43 healthy

controls. Isotype-specific enzyme-linked immunosorbent assays (ELISAs) were

used to detect NAbs against actin, myosin, keratin, desmin, troponin,

tropomyosin, thyroglobulin, insulin, single-stranded DNA and the hapten

trinitrophenyl. NAb activity was significantly higher in sera from patients

with NL (either with or without IDDM), compared with that detected in sera

from patients with IDDM which was similar to that of healthy individuals.

High proportion of NL sera exhibited increased IgG anti-tropomyosin (69%),

anti-troponin, anti-desmin and anti-keratin (50% each), anti-insulin (44%)

and anti-trinitrophenyl (31%) activities, as well as increased IgA and IgM

anti-keratin activities (26% and 31%, respectively). The great majority

(88%) of positive sera were polyreactive and contained NAbs, polyspecific

and monospecific (as demonstrated by immunoadsorption studies), belonging

to more than one isotype; there was no predominant serological reactivity

pattern. In conclusion, increased NAb activity to cytoskeleton proteins is

associated with the dermatological disease NL and not to the overlapping

autoimmune disease (IDDM). The origin and significance of these NAbs is

discussed.

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34.) An unusual case of giant dermatofibroma in a patient with diabetes

mellitus and necrobiosis lipoidica.

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Omulecki A; Skwarczynska-Banys E; Zalewska A; Wozniak L

Department of Dermatology, Medical University of Lodz, Poland.

Cutis (UNITED STATES) Oct 1996 58 (4) p282-5 ISSN: 0011-4162

Language: ENGLISH

Document Type: JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES 

Journal Announcement: 9704

Subfile: INDEX MEDICUS

A case of nine dermatofibromata, including a giant one, associated with

necrobiosis lipoidica and diabetes mellitus type II is reported. This case

is unusual because of 

the number and size of the tumors and their association with the

above-mentioned pathologic conditions. (20 References)

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (40) 22/02/99 DR. JOSE LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
Venezuela 1.998-2.024

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