Necrobiosis Lipoidica


Article Author:
Kenia Lepe


Article Editor:
Francisco Salazar


Editors In Chief:
Donald Kushner
Annabelle Dookie


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
5/5/2019 11:29:03 PM

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.

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 a multidisciplinary 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]

 

 

 


  • Image 5771 Not availableImage 5771 Not available
    Contributed by the Dermatologic Institute of Jalisco, México
Attributed To: Contributed by the Dermatologic Institute of Jalisco, México

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Necrobiosis Lipoidica - Questions

Take a quiz of the questions on this article.

Take Quiz
A 29-year-old with severe diabetes mellitus has now developed necrobiosis lipoidica. Where would one most likely see this skin lesion?

(Move Mouse on Image to Enlarge)
  • Image 322 Not availableImage 322 Not available
    Contributed by DermNetNZ
Attributed To: Contributed by DermNetNZ



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Where is necrobiosis lipoidica more frequently encountered?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which one of the following is not true of necrobiosis lipoidica diabeticorum?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is considered first-line therapy for necrobiosis lipoidica?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 40-year-old female presents with a 10-month history of a yellow, telangiectatic, asymptomatic, plaque, with central ulceration, on the pretibial surface of her left leg. She was diagnosed with type 1 diabetes mellitus at the age of 18 and is currently on treatment with long-acting and short-acting insulin. According to your clinical suspicion, how would you confirm the diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following statements regarding necrobiosis lipoidica is true?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Necrobiosis lipoidica (NL) can have a similar clinical and histological appearance to other skin diseases, particularly granuloma annulare (GA). Which of the following can help the differentiation between NL and GA?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Necrobiosis Lipoidica - References

References

Necrobiosis Lipoidica., Sibbald C,Reid S,Alavi A,, Dermatologic clinics, 2015 Jul     [PubMed]
The cutaneous immunopathology of necrobiosis lipoidica diabeticorum., Quimby SR,Muller SA,Schroeter AL,, Archives of dermatology, 1988 Sep     [PubMed]
Erfurt-Berge C,Seitz AT,Rehse C,Wollina U,Schwede K,Renner R, Update on clinical and laboratory features in necrobiosis lipoidica: a retrospective multicentre study of 52 patients. European journal of dermatology : EJD. 2012 Nov-Dec;     [PubMed]
Gebauer K,Armstrong M, Koebner phenomenon with necrobiosis lipoidica diabeticorum. International journal of dermatology. 1993 Dec;     [PubMed]
Hawryluk EB,Izikson L,English JC 3rd, Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions. American journal of clinical dermatology. 2010;     [PubMed]
Fertitta L,Vignon-Pennamen MD,Frazier A,Guibal F,Caumes E,Bagot M,Bouaziz JD,Frumholtz L, Necrobiosis lipoidica with bone involvement successfully treated with infliximab. Rheumatology (Oxford, England). 2019 Mar 15;     [PubMed]
Hashemi DA,Brown-Joel ZO,Tkachenko E,Nelson CA,Noe MH,Imadojemu S,Vleugels RA,Mostaghimi A,Wanat KA,Rosenbach M, Clinical Features and Comorbidities of Patients With Necrobiosis Lipoidica With or Without Diabetes. JAMA dermatology. 2019 Feb 20;     [PubMed]
Tong LX,Penn L,Meehan SA,Kim RH, Necrobiosis lipoidica. Dermatology online journal. 2018 Dec 15;     [PubMed]
Imadojemu S,Rosenbach M, Advances in Inflammatory Granulomatous Skin Diseases. Dermatologic clinics. 2019 Jan;     [PubMed]
Dissemond J,Erfurt-Berge C,Goerge T,Kröger K,Funke-Lorenz C,Reich-Schupke S, Systemic therapies for leg ulcers. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2018 Jul;     [PubMed]
Lause M,Kamboj A,Fernandez Faith E, Dermatologic manifestations of endocrine disorders. Translational pediatrics. 2017 Oct;     [PubMed]
Konschake W,Valesky E,Stege H,Jünger M, [Evidence of compression therapy]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2017 Aug;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Podiatry APMLE Part 3. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Podiatry APMLE Part 3, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Podiatry APMLE Part 3, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Podiatry APMLE Part 3. When it is time for the Surgery-Podiatry APMLE Part 3 board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Podiatry APMLE Part 3.