BASICS
DESCRIPTION
- Necrobiosis lipoidica (NL) presents with violaceous red " “brown plaques with palpable borders and yellow " “brown atrophic centers with telangiectasias.
- Most commonly occurs on the pretibial area
- May ulcerate after trauma
- Ulceration found in 25% of cases.
- Associated with diabetes mellitus (DM) in 46% of cases
- May persist for decades
- Management includes medical and/or surgical treatment.
EPIDEMIOLOGY
- 0.3 " “1.2% of DM patients have NL (1):
- NL precedes DM diagnosis in 14%.
- NL is diagnosed concurrently with DM in 24%.
- NL onset follows DM diagnosis in 62%.
- Female > male (3:1) (2)
- Most prevalent in ages 20 to 40 years, with earlier onset in type I DM patients; may also occur in children and elderly
ETIOLOGY AND PATHOPHYSIOLOGY
- Exact etiology remains unknown.
- One theory suggests that NL results from systemic microangiopathy associated with DM.
- Other theories include immunoglobulin deposition, tissue damage due to venous insufficiency and hypercholesterolemia, impaired neutrophil migration, collagen abnormalities, and trauma.
- Pathophysiology demonstrates collagen degeneration evolving into granulomatous inflammation with dermal and subcutaneous inflammation.
- Fatty deposition and endothelial wall thickening occurs later, secondary to inflammation.
RISK FACTORS
- DM
- Hypertension
- Obesity
- Trauma
GENERAL PREVENTION
- Smoking cessation
- Blood glucose control
- Avoidance of trauma
- Compression stockings
COMMONLY ASSOCIATED CONDITIONS
- Obesity, hyperlipidemia, hypertension, and diabetes complications, such as peripheral neuropathy, nephropathy, and retinopathy
- Also may be found with thyroid disorders, sarcoid, inflammatory bowel disease, and rheumatoid arthritis (1)
DIAGNOSIS
HISTORY
- Lesions enlarge slowly from months to years.
- Decreased sensation to pinprick and fine touch
- Ulceration occurs typically after trauma.
- Lesions, especially when ulcerated, may be painful and/or pruritic.
PHYSICAL EXAM
- Most commonly pretibial but may also be present on upper extremities, face, penis, trunk, acral surfaces, and scalp
- Initially appears as small, firm, well-circumscribed, red " “brown papules or patches
- Later coalesce into plaques and enlarge centrifugally with subsequent central epidermal atrophy.
- Chronic lesions may present with yellowing, telangiectasias, and ulceration (3).
- Partial alopecia may occur with scalp lesions.
- Usually, one to three lesions and occasionally symmetric bilaterally
DIFFERENTIAL DIAGNOSIS
- Granuloma annulare
- Sarcoidosis
- Necrobiotic xanthogranuloma
- Eruptive xanthoma
- Rheumatoid nodule
- Elastosis perforans serpiginosa
- Amyloidosis
- Pigmented purpuric dermatosis
- Stasis dermatitis
- Erythema nodosum
- Lupus panniculitis
DIAGNOSTIC TESTS & INTERPRETATION
Consider evaluating for underlying disease with HgbA1c, fasting blood glucose, or 2-hour postprandial glucose, fasting lipid panel, and/or thyroid function tests. ‚
Diagnostic Procedures/Other
Dermoscopy and a 3- to 5-mm punch skin biopsy that includes subcutaneous fat may help to differentiate from granuloma annulare, sarcoidosis, or other granulomatous disorders. ‚
Test Interpretation
- Dermoscopy
- Reveals elongated and serpentine telangiectasias and hairpin-like vessels, which are typically located over a white to yellow structure-less background (4)[B]
- Skin biopsy
- Layers of interstitial and palisaded granulomas extending throughout the dermis to the subcutaneous fat
- Degenerated collagen bundles (necrobiosis), followed by sclerosis
- Extracellular lipid deposition and fat-containing foam cells (lipoidica)
- Superficial and deep perivascular infiltrate present, with predominantly lymphocytes, as well as occasional plasma cells and eosinophils.
- No increase in mucin.
- Direct immunofluorescence may show C3, IgM, IgA, fibrin, and fibrinogen in vessel walls.
TREATMENT
GENERAL MEASURES
- Compression stockings (1)[B]
- Local wound care for ulcers
- Controversy exists, but most reports fail to show a correlation of improved NL with tighter blood glucose control (2)[C].
- Few data exist regarding the most effective medical treatment, and different therapies may be tried.
MEDICATION
First Line
- No double-blinded randomized controlled trials exist for standardized treatment (1).
- Topical triamcinolone 0.1% TID, followed by betamethasone 0.05%, or fluocinonide 0.05% BID under hydrocolloid occlusion, if no effect (1)[B]
- If no ulcer present, intralesional triamcinolone 5 mg/mL with lidocaine at advancing edges (2)[C]
- Systemic steroids tapering over 4 to 5 weeks
- Caution: Steroids may worsen atrophy and blood sugar levels, so avoid applying steroids to atrophic areas; apply to advancing edges. Monitor blood sugars when using intralesional and systemic steroids.
- Refer to a dermatologist for NL unresponsive to steroid therapy.
Second Line
- No single drug has shown consistent efficacy; data is mostly based on case reports and small case series (2,5)[C].
- Psoralen plus ultraviolet light of A (PUVA), UVA-1, photodynamic therapy (2)[C]
- Topical tacrolimus 0.1% ointment (2)[C]
- Fumaric acid esters
- Dapsone
- Pentoxifylline (2)[C]
- Aspirin, dipyridamole, and chloroquine
- Nicotinic acid
- Clofazimine (limit to 3 months) (2)[C]
- For severe, refractory ulcerative cases, granulocyte macrophage colony-stimulating factor to promote healing of ulcers (5)[C]
- Tumor necrosis factor-α inhibitors such as infliximab or etanercept (5)[C]
- Systemic cyclosporine (5)[C]
- Topical tretinoin 0.025% gel for atrophy
SURGERY/OTHER PROCEDURES
- Hyperbaric O2 in chronic ulcers
- Surgical excision for severe ulcers into deep fascia and periosteum, to prevent recurrence
- May use split-thickness grafting to promote wound healing, although poor healing is not uncommon
- Topically applied bovine collagen or becaplermin
- Pulse dye laser for erythema and telangiectasia
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Evaluate for peripheral vascular disease, including ankle-brachial index, angiographies, and venous circulation studies. ‚
Patient Monitoring
- Monitor and treat for secondary infections if lesions ulcerate.
- In patients with diabetes, monitor for complications, such as retinopathy and nephropathy (3)[C].
DIET
American Diabetic Association Diet ‚
PATIENT EDUCATION
- Smoking cessation
- Avoidance of trauma
- Elastic support stockings
- Leg rest
- Address secondary infections
- Appropriate dressings
PROGNOSIS
- Spontaneous resolution is infrequent (13 " “19% after 6 to 12 years) (5).
- Refractory cases are the rule; lesions tend to relapse once therapy is removed (5).
COMPLICATIONS
- Ulceration
- Local wound infection
- Scarring/disfigurement
- Squamous cell carcinoma (rare)
REFERENCES
11 Erfurt-Berge ‚ C, Seitz ‚ AT, Rehse ‚ C, et al. Update on clinical and laboratory features in necrobiosis lipoidica: a retrospective multicentre study of 52 patients. Eur J Dermatol. 2012;22(6):770 " “775.22 Reid ‚ SD, Ladizinski ‚ B, Lee ‚ K, et al. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol. 2013;69(5):783 " “791.33 Hawryluk ‚ EB, Izikson ‚ L, English ‚ JCIII. Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions. Am J Clin Dermatol. 2010;11(3):171 " “181.44 Pellicano ‚ R, Caldarola ‚ G, Filabozzi ‚ P, et al. Dermoscopy of necrobiosis lipoidica and granuloma annulare. Dermatology. 2013;226(4):319 " “323.55 Murphy-Chutorian ‚ B, Han ‚ G, Cohen ‚ SR. Dermatologic manifestations of diabetes mellitus: a review. Endocrinol Metab Clin North Am. 2013;42(4):869 " “898.
ADDITIONAL READING
- Bonura ‚ C, Frontino ‚ G, Rigamonti ‚ A, et al. Necrobiosis lipoidica diabeticorum: a pediatric case report. Dermatoendocrinol. 2014;6(1):e27790.
- Davison ‚ JE, Davies ‚ A, Moss ‚ C, et al. Links between granuloma annulare, necrobiosis lipoidica diabeticorum and childhood diabetes: a matter of time? Pediatr Dermatol. 2010;27(2):178 " “181.
- Kosaka ‚ S, Kawana ‚ S. Case of necrobiosis lipoidica diabeticorum successfully treated by photodynamic therapy. J Dermatol. 2012;39(5):497 " “499.
- Kota ‚ SK, Jammula ‚ S, Kota ‚ SK, et al. Necrobiosis lipoidica diabeticorum: a case-based review of literature. Indian J Endocrinol Metab. 2012;16(4):614 " “620.
- P „ ƒtra … Ÿcu ‚ V, Giurc „ ƒ ‚ C, Ciurea ‚ RN, et al. Ulcerated necrobiosis lipoidica to a teenager with diabetes mellitus and obesity. Rom J Morphol Embryol. 2014;55(1):171 " “176.
- Su ƒ ¡rez-Amor ‚ O, Perez-Bustillo ‚ A, Ruiz-Gonz ƒ ¡lez ‚ I, et al. Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to etanercept and a review of the literature. Dermatology. 2010;221(2):117 " “121.
- Tauveron ‚ V, Rosen ‚ A, Khashoggi ‚ M, et al. Long-term successful healing of ulcerated necrobiosis lipoidica after topical therapy with becaplermin. Clin Exp Dermatol. 2013;38(7):745 " “747.
- Thomas ‚ M, Khopkar ‚ US. Necrobiosis lipoidica: a clinicopathological study in the Indian scenario. Indian Dermatol Online J. 2013;4(4):288 " “291.
CODES
ICD10
- L92.1 Necrobiosis lipoidica, not elsewhere classified
- E10.620 Type 1 diabetes mellitus with diabetic dermatitis
- E11.620 Type 2 diabetes mellitus with diabetic dermatitis
ICD9
- 709.3 Degenerative skin disorders
- 250.81 Diabetes with other specified manifestations, type I [juvenile type], not stated as uncontrolled
- 250.80 Diabetes with other specified manifestations, type II or unspecified type, not stated as uncontrolled
SNOMED
- Necrobiosis lipoidica
- Necrobiosis lipoidica diabeticorum (disorder)
CLINICAL PEARLS
- NL is associated with abnormal glucose tolerance, but progression does not typically correlate with glucose control.
- Patients should avoid trauma and provide local wound care.
- Diagnostic studies should be performed for suspected peripheral vascular disease.