Quick Diagnosis
Farheen Mussani, BHSc. (1T1), Faculty of Medicine, University of Toronto
Maxine Yat Wing Wong, MD, MRCP (U.K.), FRCPC, Faculty of Medicine, University of Toronto
A 25-year-old woman presented with asymptomatic large yellowish lesions on both shins. The
lesions began as small red bumps and developed into the current larger lesions over the course of
one year. She was otherwise well, apart from a history of type 2 diabetes mellitus. Her
medications were metformin and glyburide. There was no history of smoking or alcohol
ingestion and her family history was unremarkable for any skin conditions.
On examination, the lesion on the right shin measured 5.0 x 3.0 cm and the lesion on the left
shin was 4.5 x 3.0 cm in size. They were yellowish plaques with erythematous borders.
Telangiectasia were noted in the central atrophic area. Ulceration was not seen and the lesions
were non-tender. The rest of the skin appeared normal.
A skin biopsy from the lesion on the right shin was performed. Histology showed an atrophic
epidermis. There were palisaded granulomas involving both the dermis and subcutaneous tissue
with necrobiosis of collagen. Occasional eosinophils and plasma cells were present. There was
no evidence of vasculitis.
What is the diagnosis?
And the diagnosis is…
Necrobiosis Lipoidica
Necrobiosis lipoidica (NL) was first described by Oppehhein in 19291. It is a rare chronic
granulomatous dermatosis that usually develops in patients aged 30-40 years. The prevalence
ratio of females to males is 3:11,2. While the etiology of the disease is unknown, studies have
shown that approximately 75% of patients with NL have diabetes or glucose intolerance.2
However, the prevalence of NL in diabetes is very low, between 0.3% - 3%1,2. Diabetes patients
with NL tend to have an increased rate of end-organ damage3. It is uncertain whether tighter
glycemic control will improve NL.3 NL has also been associated with Crohn’s disease, ulcerative
colitis, sarcoidosis, rheumatoid arthritis, autoimmune thyroid disease and granuloma annulare2.
The lesions appear predominantly on the lower legs, especially in the pretibial region. However,
some patients may develop NL on the dorsum of the hands, forearms, trunk and scalp. Rarely,
NL can be localized to the penis4. Lesions frequently start as red papules or nodules and grow
into plaques with atrophic yellowish waxy centres and an erythematous border. Telangiectasia
often are evident. Koebner phenomenon and perforating lesions have been described in NL1,4.
NL is often asymptomatic; however, pain is associated frequently with ulceration. Ulceration
can occur de novo, as a result of trauma or with intralesional steroid therapy. Longstanding
ulceration is a risk factor for the rare development of squamous cell carcinoma1,2. Approximately
20% of patients experience spontaneous remission1.
Etiology of NL is unclear and several mechanisms have been proposed. First, deposition of
glycoprotein or deposition of immunoglobulins, complement C3 and fibrin may induce vascular
damage. Second, increased collagen cross-links may result in basement membrane thickening.
Third, trauma and metabolic changes also may play a role1.
Differential Diagnosis:
When necrobiosis lipoidica is suspected, the clinician should consider the following in their
differential diagnoses:

Granuloma Annulare

Sarcoidosis

Xanthoma
Investigations:
Blood tests may reveal an elevated blood glucose and HbA1c.
On histopathological examination of necrobiosis lipoidica, there are characteristic palisaded
granulomas in the dermis which may extend into the subcutaneous tissue. On low magnification,
one can appreciate that the granulomas and collagen degeneration (necrobiosis) are arranged in
alternate layers1,4. Furthermore, superficial and deep perivascular lymphocytes, a plasma cell
infiltrate and dermal fibrosis may also be seen. Occasionally, eosinophils are present1,4.
In necrobiosis lipoidica, the epidermis may be normal, atrophic or ulcerated. There are often
vascular changes such as endothelial swelling or perivascular lymphocytic infiltrates in the deep
dermal vessels. Cholesterol clefts and transepidermal elimination are uncommon associated
features.
On direct immunofluorescence (DIF) microscopy, IgM, IgA, C3 and fibrinogen may be found in
the blood vessels in some cases of NL. Such changes are primarily seen in NL associated with
diabetes mellitus1. These findings are nonspecific and DIF is not routinely performed in the
investigation of patients with NL.
Treatment:
The evidence for using any therapies to treat NL is largely anecdotal. There have been case
reports and uncontrolled case studies on many different therapeutic regimens1.
As most NL lesions are asymptomatic, the primary aim of therapy is to prevent the development
of ulceration. In this regard, the use of elastic support stockings and avoidance of trauma are
beneficial1. Although potent topical steroids under occlusion and intralesional steroids can be
used to slow progression of NL, the latter can sometimes lead to ulceration1.
The uncontrolled studies of anti-malarials5, fumaric acid esters6 and PUVA7 in the treatment of
NL have reported good success rate. Photodynamic therapy, on the other hand, was not as
promising and frequently causes discomfort during treatment sessions8. Other therapeutic options
from anecdotal reports include anti-platelet agents such as acetylsalicylic acid, dipyridamole,
ticlodipine and pentoxyfylline, anti-tumor necrosis factor agents such as thalidomide, etanercept
and infliximab4. Methotrexate in combination with cyclosporine and pentoxyfylline were
successful in one case of recalcitrant NL9.
In patients whom ulceration is present, topical tacrolimus ointment, cyclosporine, topical PUVA
and infliximab have been reported to be useful1.
References:
1.
Barnes CJ, Davis L. Necrobiosis lipoidica. eMedicine Online. Updated Jul 31, 2009.
Accessed Nov 19, 2009 at http://emedicine.medscape.com/article/1103467-overview.
2.
Peyrí J, Morena A, Marcoval J. Necrobiosis lipoidica. Semin Cutan Med Surg.
2007;26(2):87.
3.
Cohen O, Yaniv R, Karasik A, et al. Necrobiosis lipoidica and diabetic control revisited.
Medical Hypotheses 1996;46:348-50
4.
Ghazarian D, Al Habeeb A. Necrobiotic lesions of the skin: approach and review of
literature. Diagnostic Histopathol. 2009;15(4):186.
5.
Durupt F, Dalle S, Debarbieux S, et al. Successful treatment of necrobiosis lipoidica with
antimalarial agents. Arch Dermatol 2008;144(1):118-9
6.
Kreuter A, Knierim C, Stucker M, et al. Fumaric acid esters in necrobiosis lipoidica:
results of a prospective noncontrolled study. Br J Dermatol 2005;153:802-7
7.
Patel GK, Mills CM. A prospective open study of topical psoralen-UV-A therapy for
necrobiosis lipoidica. Arch Dermatol 2001;137:1658-60
8.
Berking C, Hegyi J, Arenberger P, et al. Photodynamic therapy of necrobiosis lipoidica –
A multicenter study of 18 patients. Dermatology 2009;218:136-9
9.
West EA, Warren RB, King CM. A case of recalcitrant necrobiosis lipoidica responding
to combined immunosuppression therapy. J Euro Acad Dermatol Venereol 2007;21:830-1
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