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****** DATA-MEDICOS **********
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NECROBIOSIS LIPOIDICA DIABETICORUM 
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****** DERMAGIC-EXPRESS No.40 ******* 
****** 22 FEBRERO DE 1.999 ********* 
22 FEBRUARY 1.999
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EDITORIAL ESPAÑOL
=================
Hola amigos DERMAGICOS, en la edicion de hoy, una revision sobre el tema
NECROBIOSIS 
LIPOIDICA DIABETICORUM, bastante dificil de tratar por cierto. Estas 34
referencias bibliograficas nos actualizan sobre esta compleja patologia,
manifestacion clinica 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, encontre varios articulos interesantes sobre la
DERMATOSCOPIA, motivo de la proxima edición, saludos Argentina. 

Hasta la proxima edición: LA DERMATOSCOPIA. 

Saludos a TODOS,,, 

Dr. Jose 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,
======================================================================
DERMAGIC/EXPRESS(40)
======================================================================
NECROBIOSIS LIPOIDICA DIABETICORUM
======================================================================
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.

========================================================================
1.) Necrobiosis lipoidica diabeticorum: a clinicopathologic study. 
========================================================================
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. 

========================================================================
2.) Ulcerated necrobiosis lipoidica diabeticorum in a patient with a
history of generalized granuloma annulare. 
========================================================================
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. 

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

========================================================================
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. 

========================================================================
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. 

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

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

========================================================================
8.) Perforating elastosis in necrobiosis lipoidica diabeticorum. 
========================================================================
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. 

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

========================================================================
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. 

========================================================================
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. 

========================================================================
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. 

========================================================================
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. 

========================================================================
14.) Necrobiosis lipoidica and diabetic control revisited. 
========================================================================
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. 

========================================================================
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. 

========================================================================
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. 

========================================================================
17.) [Ulcerated necrobiosis lipoidica associated with insulin-dependent
diabetes mellitus. Beneficial effect of corticosteroid therapy by oral
administration] 
========================================================================
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. 

======================================================================
18.) Treatment with benzoyl peroxide of ulcers on legs within lesions of
necrobiosis lipoidica diabeticorum.
======================================================================
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.

======================================================================
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.

======================================================================
20.) Necrobiosis lipoidica. An immunofluorescence study.
======================================================================
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.

======================================================================
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.

======================================================================
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.
======================================================================
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.]
======================================================================
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.
======================================================================
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.
======================================================================
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-MEDICOS/DERMAGIC-EXPRESS No (40) 22/02/99 DR. JOSE LAPENTA R. 
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