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Necrobiosis Lipoidica

BASICS

DESCRIPTION

- 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.

  • 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

  • DermoscopyReveals elongated and serpentine telangiectasias and hairpin-like vessels, which are typically located over a white to yellow structure-less background (4)[B]
  • Skin biopsyLayers of interstitial and palisaded granulomas extending throughout the dermis to the subcutaneous fatDegenerated collagen bundles (necrobiosis), followed by sclerosisExtracellular 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.