Necrobiosis Lipoidica
- Article Author:
- Kenia Lepe
- Article Author:
- Christopher Riley
- Article Editor:
- Francisco Salazar
- Updated:
- 9/15/2020 7:34:22 PM
- For CME on this topic:
- Necrobiosis Lipoidica CME
- PubMed Link:
- Necrobiosis Lipoidica
Introduction
Necrobiosis lipoidica (NL) is a rare, chronic, idiopathic, granulomatous disease of collagen degeneration with the risk of ulceration, classically associated with diabetes mellitus, usually, type 1.
Etiology
The cause of necrobiosis lipoidica remains unknown. Elements of a vascular disturbance involving immune complex deposition or microangiopathic changes leading to collagen degeneration have been the most common theories. [1] Some investigators consider necrobiosis lipoidica to be primarily a disease of collagen, with inflammation occurring as a secondary event.
Epidemiology
Necrobiosis lipoidica has an increased prevalence in individuals with diabetes, although this association is currently questioned. The incidence among people with diabetes is only 0.3% to 1.2%. Necrobiosis lipoidica precedes diabetes in up to 14% and appears simultaneously in up to 24% and occurs after diabetes is diagnosed in 62% of cases. There is no proven connection between the level of glycemic control and the likelihood of developing necrobiosis lipoidica.
Although it may present in healthy individuals with no underlying disease, other commonly associated conditions are thyroid disorders and inflammatory diseases, such as Crohn disease, ulcerative colitis, rheumatoid arthritis, and sarcoidosis. In one series, researchers found surprisingly lower rates of arterial hypertension than in the standard population, while obesity and fatty acid disorders were at a standard rate. No evidence for the induction of necrobiosis lipoidica by infection or underlying malignancies was found among those patients.
There appears to be a predominance of 77% in females. [2] Also, the onset in women is younger than in men. Necrobiosis lipoidica has an average age of onset between 30 and 40 years.
Pathophysiology
An immunologically mediated vascular disease has been suggested as the primary cause of the altered collagen. The most common vascular abnormalities seen in necrobiosis lipoidica lesions are thickening of the vessel walls, fibrosis and endothelial proliferation leading to occlusion in the deeper dermis, especially in patients with diabetes. Deposition of fibrin, IgM, and C3 at the dermo-epidermal junction of blood vessels has been shown in immunofluorescence studies. [3]
The concentration of collagen decreases in necrobiosis lipoidica, and electron microscopy shows a loss of the cross-striations of collagen fibrils and important variation in the diameter of individual fibrils. Fibroblasts cultured from necrobiosis lipoidica synthesize less collagen than their counterparts from the unaffected skin.[4]
Granuloma formation has been thought to occur as a result of defective neutrophil migration allowing macrophages to take on the neutrophil role and accumulate with subsequent granuloma formation.
Histopathology
Histopathologically biopsy specimens, from the palpable inflammatory border, reveal scattered palisaded and interstitial granulomatous dermatitis with layered tiers of granulomatous inflammation parallel to the skin surface involving the entire dermis and extending into the subcutaneous fat septae. The epidermis is normal or atrophic. Focal loss of elastic tissue can be demonstrated in areas of connective tissue sclerosis. There is no significant mucin deposition in the center of the palisading granulomas, in contrast to granuloma annulare.
History and Physical
Necrobiosis lipoidica (NL) is characterized by yellow-brown, atrophic, telangiectatic plaques with an elevated violaceous rim, typically present in the pretibial surface. Less typical anatomic locations include the upper extremities, face, and scalp, where lesions may be more straight or wavy and are less weakened.
Lesions usually begin as small, firm, red-brown papules that gradually enlarge and then develop central epidermal atrophy. Ulceration occurs in approximately a third of lesions, usually following minor trauma. The plaques are usually multiple and bilateral. These lesions can Koebnerize if they are traumatized. Therefore, surgical treatments represent a challenge.
The disease course appears more severe in men as they have a higher likelihood of ulceration in their lesions, reported in 58% of males vs. 15% of females. Decreased sensation to pinprick and fine touch, hypohidrosis and partial alopecia can be found within NL plaques. Rare reports show squamous cell carcinoma developing within lesions of NL.
Evaluation
Although the diagnosis often is based on clinical examination, a biopsy should be performed to differentiate necrobiosis lipoidica from conditions with similar clinical appearances, including granuloma annulare and necrobiotic xanthogranuloma.
If there is a concern for venous disease or peripheral arterial disease, further studies should be considered. Baseline blood work should include a fasting blood glucose or glycosylated hemoglobin to screen for diabetes or assess glycemic control in patients known to have diabetes. If these are not diagnostic, they should be repeated on a yearly basis, as necrobiosis lipoidica can be the first presentation of diabetes.
The differential diagnosis includes mainly granuloma annulare, necrobiotic xanthogranuloma, sarcoidosis, diabetic dermopathy, and lipodermatosclerosis. Lesions of granuloma annulare and sarcoidosis generally do not exhibit the same degree of atrophy, telangiectasias or yellow-brown color. Additionally, the appearance of lipid and decreased amount of mucin in necrobiosis lipoidica helps to differentiate from granuloma annulare. [5]
Treatment / Management
No treatment has proven to be effective. In patients with diabetes mellitus, control of blood glucose usually does not have a significant effect on the course. In the absence of ulceration or symptoms, it is reasonable not to treat necrobiosis lipoidica given that up to 17% of lesions may resolve spontaneously. Compression therapy controls edema and promotes healing in patients with associated venous disease or lymphedema.[6][7][8]
When ulcerations are present, proper wound care principles are important. First-line therapy includes potent topical corticosteroids for early lesions and intralesional corticosteroids injected into the active borders of established lesions. For inactive, atrophic lesions, topical steroids should be avoided as they may exacerbate the atrophy and increased risk of new ulcerations.
Ultraviolet (UV) light therapy is used for various inflammatory dermatoses. PUVA decreases the actively inflamed borders but has no clinical effects on atrophic scars.
Calcineurin inhibitors inhibit T-cell activation by blocking calcineurin resulting in both anti-inflammatory and immunomodulatory effects. Topical tacrolimus has been shown to be effective in resolving ulceration associated with necrobiosis lipoidica.[9][10][11]
TNF is an important regulator of the formation of granulomas. The monoclonal antibodies adalimumab and infliximab bind directly to soluble TNF-alpha to prevent its action. Etanercept is a fusion protein made up of the Fc portion of human IgG1 and TNF receptors that also inhibit TNF function. Both etanercept and infliximab have been repeatedly effective as monotherapy for ulcerating necrobiosis lipoidica.
Differential Diagnosis
- Acute complications of sarcoidosis
- Granuloma annulare
- Hematologic malignancies
- Paraproteinemia
- Rheumatoid arthritis
- Sarcoidosis
- Ulcerated necrobiotic
- Xanthogranuloma
- Xanthomas
Pearls and Other Issues
Ulcerative skin lesions may complicate the course of the disease, especially in patients with diabetes, but also in patients with arterial hypertension and/or those who are overweight. There is no data to support any preventive measure for necrobiosis lipoidica.
Enhancing Healthcare Team Outcomes
NL is a rare skin complication of type 1 diabetes. However, its diagnosis and management is exceedingly difficult. The skin lesions are best managed with an interprofessional team that includes a dermatologist, endocrinologist, wound care nurse, internist and an infectious disease specialist. There is no specific treatment for NL. The key is to ensure that the diabetes is well controlled. Open wounds and ulcers need to be managed by a wound care nurse. Many newer biological agents have been used to treat the skin disorder but without clinical trials, it is difficult to know the effectiveness of these agents. These patients need long term follow up as the wound closure can take months. Some people may benefit from compression therapy and stockings.[12]
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Necrobiosis lipoidica
Contributed by the Dermatologic Institute of Jalisco, México