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.     

糖尿病性类脂质渐进性坏死1例

报告1例糖尿病性类脂质渐进性坏死。患者男，37岁。左足背和右裸关节处褐色斑块4年余，逐渐增大，边缘隆起，中央无萎缩，局部无瘙痒和疼痛。否认有局部外伤和化学物质接触史。无家族性糖尿病病史。尿糖（ ），糖耐量试验异常。皮损组织病理检查典型的类脂质渐进性坏死特征。随着糖尿病的控制，皮疹逐渐消退。     

Skin sarcoidosis simulating necrobiosis lipoidica

A patient who had had pulmonary sarcoidosis for 11 years developed multiple symmetrical lesions with ulcerations on the lower legs. The lesions showed the typical clinical picture of necrobiosis lipoidica and could not be differentiated histologically with certainty. Three years later persistent reddish plaques appeared on both arms, which allowed clinical and histological diagnosis of cutaneous sarcoidosis.     

Cutaneous signs of lymphomatoid granulomatosis

A retrospective review of 47 cases of lymphomatoid granulomatosis encountered between 1977 and 1990 revealed that 24 patients had skin involvement. Clinical and histologic features were noted. The dominant and most characteristic cutaneous finding was scattered nodules. Other cutaneous changes included eroded and crusted lesions, facial edema, papules, and folliculitis-like eruptions. The nodular skin lesions most often had an angiocentric and angiodestructive dense, polymorphous, lymphohistiocytic infiltrate in the dermis and fat. A minority of the cases had a lymphoma cutis type of infiltrate. Immunophenotypic analysis showed a mixed population of T cells, with helper T cells (CD4+) predominant. Our results emphasize the usefulness of the clinical and histologic examination of the skin in lymphomatoid granulomatosis. The histologic pattern of lymphomatoid granulomatosis was seen in the skin in more than half of the biopsy specimens.     

Necrobiosis lipoidica of the glans penis

We report a 65-year-old diabetic man with necrobiosis lipoidica occurring on the glans of penis. He was initially seen with chronic ulcerative balanitis that eventually healed with strict control of diabetes mellitus, cystostomy, and pentoxifylline, leaving heavily depressed scars. Penile necrobiotic palisading granulomas include necrobiosis lipoidica and granuloma annulare. On the basis of the literature review, these 2 diseases manifest different skin lesions.     

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

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

Primary and isolated cutaneous lymphomatoid granulomatosis following heart-lung transplantation

BACKGROUND: Lymphomatoid granulomatosis is an Epstein-Barr virus-associated B-cell lymphoproliferative disease. It is angiocentric and angiodestructive and involves the lungs, central nervous system and skin. Exclusive cutaneous involvement is rare and may be associated with a better outcome. Contrarily to the extra-cutaneous forms of lymphomatoid granulomatosis, it is difficult or impossible to detect Epstein-Barr virus DNA sequences in primary and isolated cutaneous lymphomatoid granulomatosis. CASE REPORT: A 54-year-old woman developed erythemato-violaceous lesions on both legs 3 years after a heart-lung transplantation. The diagnosis of erythema multiforme and of drug-induced vasculitis were first made. Because of fever and of the rapid extension of the lesions, the patient was hospitalized. The histologic examination of the first lesions showed a perivascular infiltrate, without epidermotropism, composed of histiocytes, lymphocytes and plasma cells. Immunohistochemistry revealed the presence of a predominantly T-cell infiltrate with some large B cells. Subsequent biopsies were diagnosed as high grade B-cell lymphoma. Polymerase chain reaction analysis as well as in situ hybridation study showed the presence of Epstein-Barr virus load in the lesions. There was however no serologic evidence of viral reactivation. Extensive systemic evaluation revealed no visceral or bone marrow involvement. Despite antiviral treatment and CHOP polychemotherapy, the patient died 3 months after her admission. DISCUSSION: This observation of lymphomatoid granulomatosis is particular because of its exclusive cutaneous involvement associated with a fulminant evolution to high grade B lymphoma. The presence of a context of iatrogenic immunosuppression underlies the role of altered immune cellular functions in the initiation and/or progression of lymphomatoid granulomatosis and strengthens the role of a viral agent in its pathogenesis. We suggest that the presence of Epstein-Barr virus, which is generally not associated with the isolated cutaneous forms of lymphomatoid granulomatosis, may have played a role in this fulminant evolution to high grade B lymphoma.     

Cutaneous Sarcoidosis Clinically Mimicking Necrobiosis Lipoidica in a Patient with Systemic Sarcoidosis

A 70-year-old woman with an 8-year history of systemic sarcoidosis developed round, red-brown eruptions, with central atrophic lesions on her lower legs. The features of the biopsy specimen resembled those of necrobiosis lipoidica (NL), but although necrobiosis was present there were well-formed non-necrotizing granulomas in the dermis. The histological diagnosis was cutaneous sarcoidosis. Systemic sarcoidosis presenting with NL has rarely been reported. The histological features of cutaneous sarcoidosis sometimes mimic those of other granulomatous diseases, including NL and granuloma annulare, which are difficult to distinguish. We discuss the novel association between sarcoidosis and other granulomatous diseases.     

Lymphokines (MIF) in the serum of patients with sarcoidosis and cutaneous granuloma annulare

Serum MIF activity was studied in ten patients with sarcoidosis, fourteen with granuloma annulare, four with necrobiosis lipoidica, and nine with various dermatological diseases. Positive MIF activity was found in the sera of nine of the ten patients with sarcoidosis and eleven of the fourteen patients with granuloma annulare. The delayed hypersensitivity tests were negative in all nine of the patients with sarcoidosis who had serum MIF activity and were positive in only three patients with cutaneous sarcoid lesions. One of four patients with necrobiosis lipoidica demonstrated minimal serum MIF activity. Data on serum lymphokine activity in sarcoidosis and granuloma annulare suggest that these two diseases are related to delayed hypersensitivity mechanisms.     

Differential diagnosis of granulomatous skin diseases]

The case histories of two female patients with granulomatosis disciformis and necrobiosis lipoidica are reported. Widespread skin manifestations, also in face and neck, with peculiar anular lesions complicated the differential diagnostic discrimination from sarcoidosis. The aspects of the cases and their progress are discussed in regard to the necessity of permanent checking of diagnostic preconditions during therapy.     

Necrobiosis Lipoidica-like Skin Lesions in Systemic Sarcoidosis

A 62-year-old woman with systemic sarcoidosis developed erythematous plaques on her lower legs. Clinically, two kinds of skin lesions were distinguished; one type formed brownish-red plaques with induration suggesting plaque-type skin sarcoid, and the other formed purplish erythematous plaques with atrophic centers resembling necrobiosis lipoidica. In spite of this clinical appearance, a biopsy specimen from one of the latter lesions revealed typical skin sarcoid histology composed of discrete non-caseating granulomas, while that from one of the other lesions showed necrobiotic changes of collagen bundles surrounded by epitheloid histiocytes and foreign-body giant cells. Because cutaneous involvement of sarcoidosis may mimic necrobiosis lipoidica clinically and/or histologically, we diagnosed her skin lesions as necrobiosis-like skin sarcoid.     

Necrobiosis lipoidica

A 69-year-old patient presented with different skin lesions all of which belonged to group of necrobiosis lipoidica. The initial histologic diagnosis was actinic granuloma O??Brien. A subsequent biopsy was interpreted as granulomatous necrobiosis lipoidica. The history of these necrobiotic variants is reviewed and exemplarily depicted with this case. Necrobiosis lipoidica is part of the spectrum of granulomatous skin disorders. Although its etiology is unclear, an association with diabetes mellitus is often discussed. Multiple therapeutic options exist, but standardized guidelines for treatment are missing.     

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.     

Cutaneous manifestations of Wegener granulomatosis.

In a series of 19 patients (15 male and 4 female) who had Wegener granulomatosis with specific cutaneous histopathologic findings, the skin was only involved at onset in two. Four distinct histologic subgroups were defined as follows: necrotizing vasculitis (11 patients); necrotizing palisading granuloma (Churg-Strauss lesion) 2 patients); granulomatous vasculitis (2 patients); and lymphomatoid granulomatosis (4 patients). The 11 patients with necrotizing vasculitis had purpuric and hemorrhagic lesions, and the presence of vesicles and ulceration correlated with the severity of onset and extent of disease. The remaining eight patients had papular and nodular lesions. The patients with necrotizing vasculitis and lymphomatoid granulomatosis had a worse prognosis that did those with a predominant granulomatous reaction.     

Necrobiosis lipoidica mimicking cellulitis

A 57-year-old obese patient presented with a 5 month history of tender, indurated, erythematous plaques with superficial ulceration on the right shin. The lesions closely mimicked cellulitis but were unresponsive to antibiotics. Though the patient was not a known diabetic, on investigations she was found to be a diabetic. Histology confirmed the diagnosis of necrobiosis lipoidica. This acutely inflammed presentation of necrobiosis lipoidica is extremely rare.     

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.     

Cutaneous lesions of lymphomatoid granulomatosis

Lymphomatoid granulomatosis is a rare multisystem disease involving the lungs, skin, and nervous system. The cutaneous disease may be the presenting complaint. A case with nodular and annular infiltrated lesions is reported to encourage the inclusion of lymphomatoid granulomatosis in the differential diagnosis of similar lesions. Prompt diagnosis and early long-term treatment with cyclophosphamide and prednisone can lead to prolonged remissions of this disease. If relapse occurs, prompt treatment with the same regimen may again induce a remission.     

Necrobiosis lipoidica. Variants on a theme

A 69-year-old patient presented with different skin lesions all of which belonged to group of necrobiosis lipoidica. The initial histologic diagnosis was actinic granuloma O'Brien. A subsequent biopsy was interpreted as granulomatous necrobiosis lipoidica. The history of these necrobiotic variants is reviewed and exemplarily depicted with this case. Necrobiosis lipoidica is part of the spectrum of granulomatous skin disorders. Although its etiology is unclear, an association with diabetes mellitus is often discussed. Multiple therapeutic options exist, but standardized guidelines for treatment are missing.