Perforating necrobiosis lipoidica in a girl with type 1 diabetes mellitus: A new case reported
Dermatology Department, Military Hospital of Tunis, Tunis, Tunisia. email@example.com
Necrobiosis lipoidica is an idiopathic dermatological condition that is strongly associated with diabetes mellitus. It is more commonly seen in women than men. The average age of onset is 30-40 years. Necrobiosis Lipoidica diabeticorum is an extremely rare finding in childhood diabetes. We describe the case of a 13-year-old girl who has had type 1 diabetes mellitus since she was 8 years old. The patient presented with 2 well-defined, persistent plaques with a depressed central area and elevated purple peripheral ring, one on the right thigh and the other over the lateral left leg. Histopathologic evaluation of the patient's biopsy confirmed the diagnosis of necrobiosis lipoidica with transfollicular elimination. Our patient is the second pediatric case described with perforating necrobiosis lipoidica. We review the literature and discuss clinical features, several complications, and the most recent treatment options for necrobiosis lipoidica in diabetic children.
Necrobiosis lipoidica (NL) is an idiopathic dermatological condition that is strongly associated with diabetes mellitus (DM). It is more commonly seen in women than men. The average age of onset is 30-40 years . Necrobiosis lipoidica diabeticorum (NLD) is an extremely rare finding in childhood diabetes . We report one case in a diabetic patient and review the literature.
A 13-year-old girl had type 1 diabetes mellitus since she was 8 years old. Her paternal great-grandmother and her father had type 2 diabetes mellitus. Screening for microangiopathic complications was repeated every year and negative for microalbuminuria and retinopathy. The patient's diabetes was controlled with subcutaneous insulin, 1 unit/kg body weight/day, split two-thirds in the morning (two thirds Insulatard®, one third Actrapid®) and one third in the evening (one-half Insulatard®, one half Actrapid®). The patient presented with two well-defined, persistent plaques with a depressed central area and elevated purple peripheral ring, one on the right thigh and the other over the lateral left leg. The upper lesion was a circular, indurated red plaque measuring 3.2 cm x 3.8 cm with a silvery-white, dry scale (Fig. 1). The lower lesion was a red plaque of 3.1 cm x 3.7 cm with sclerotic center and multiple hyperkeratotic plugs on the surface (Fig. 2). These plaques started as painless, reddish papules that slowly enlarged to plaques over a period of 4 months. The lesions are not near insulin injection sites.
Histopathologic evaluation of patient biopsy confirmed the diagnosis of necrobiosis lipoidica (Fig. 3 & 4) and showed transfollicular elimination of necrotic material (Fig.5). One month later, a new plaque of NL appeared on the lateral right leg of the patient.
Necrobiosis Lipoidica is a chronic granulomatous dermatosis with a prevalence of 0.3 percent in diabetic adults . However, it is also seen in patients with no detectable disturbance of glucose metabolism. It is more common in women and its onset is usually in young or middle adulthood .
It is usually considered a dermatologic marker for diabetes mellitus but is not pathognomonic for this disease. Muller and Winkelmann found that 90 percent of patients with NL are diabetic, will develop diabetes, or have a family history of diabetes . Actually, there is some controversy regarding the degree of this association. In a retrospective review of 65 patients with NL, O'Toole et al. found that only 11 percent had DM at presentation . Dandona et al. studied glycosylated hemoglobin levels in 22 patients with NL and found no correlation between the two variables . Therefore, it would appear that the strength of this association may previously have been overestimated.
Several studies suggest that there is no effect of glucose control on either the appearance of NLD or the clinical course of the lesion . Cohen et al. conclude on the contrary, that NLD is usually associated with poor glucose control and that tighter glucose control, as currently practiced, might improve or prevent this disorder .
Only a few instances have been reported of an association between NL and diabetes in children. De Silva et al. in a study of 1557 patients under the age of 15 years with type 1 DM found only one patient (0.06%) with confirmed NL . Pestoni et al., in a review of reported cases of NL in children, found that it seems to be more common in girls (at least 8 of 11 cases). Most lesions occur on the lower extremities. All the reported children had type 1 DM, except one case without DM and one who had type 2 DM .
A recent review published by Marchetti et al. seems to relate NL specifically to maturity-onset diabetes of the young (MODY). The authors report 1 case of a 12-year-old girl with granuloma annulare localized to both ankles and NL in the left pretibial region. Both occurred before the diagnosis of MODY; through a review of all the cases reported they conclude that NL appears to be more common in type 1 DM (6.5%) and in MODY (2.8%) than in type 2 DM (0.4%) .
Necrobiosis lipoidica has a characteristic clinical appearance. The eruption begins as an oval violaceous patch and expands slowly. The advancing border is red and the central area turns yellow-brown. The central area atrophies and has a waxy surface; telangiectasias become prominent . Pathologically, the lesions show degeneration of collagen, granulomatous inflammation of subcutaneous tissues and of blood vessels, capillary basement membrane thickening, and obliteration of vessel lumina . Transepithelial elimination of degenerated collagen through the hair follicle in necrobiosis lipoidica is rare, clinically manifesting as multiple hyperkeratotic plugs on the surface of the NL lesion as observed in our patient. Ten cases of perforating NL have been reported all ages included. Our patient is the second pediatric case described of perforating NL in a child with type 1 diabetes mellitus .
The most commonly affected site in NL is the leg; 85 percent of cases affect that site exclusively. Other locations, however, may include the hands, fingers, forearms, face, and scalp. The presence of multiple lesions is very rare .
We may expect to see more severe complications and attendant morbidity secondary to NL in the pediatric age range. In fact, ulceration in NL, sometimes with subsequent infection, is a frequent complication, occurring in up to 25-33 percent of the patients. However, malignant ulceration is rare, but should always be suspected when the ulcer fails to heal despite conservative measures . A case is reported of a 28-year-old type 1 diabetic woman presented with established DM in whom squamous cell carcinoma developed in an area of NL of 11 years duration .
Moreover, Verroti et al. studying diabetic children with NL, found that patients with NLD had a higher frequency of persistent microalbuminuria (p<0.001) and retinopathy (p<0.001) than those without NLD. They suggest that children as well as adult diabetics with NL can be at high risk for nephropathy and retinopathy .
Treatment of NL is challenging and often unsuccessful. First-line therapies include smoking cessation and diabetic control . In addition, topical and intralesional corticosteroids may be effective. Second-line treatments include systemic corticosteroids, cyclosporine, ticlopidine, nicotinamide, and clofazimine. Pulsed dye lasers can improve the appearance of telangiectasias . Fumaric acid esters seem to be a promising therapeutic option for patients with active NL not responding to topical or intralesional corticosteroids . In a recent study, 10 patients were treated with a 0.005 percent aqueous solution of 8-methoxypsoralen, applied topically for 30 minutes and subsequently irradiated with UVA 3 times weekly. All the patients experienced almost complete remission (after a mean of 47 sessions) . Topical tacrolimus is an effective therapeutic option in patients with ulceration due to NL. It seems to work more effectively on damaged skin with impaired barrier function, due to enhanced drug penetration, rather than on relatively intact or thickened surfaces . Zeichner J et al. obtained success with intralesional etanercept for NL in a 35-year-old woman over a period of 8 months . Beattie, PE et al. treated 6 patients with NL with a high-output ultraviolet (UV) A1 and they conclude that UVA1 carries an acceptable risk-benefit ratio and may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids and as a second-line alternative to other phototherapies .
However, NL in children can be hard to manage and may be associated with a long-term risk of malignant transformation to squamous cell carcinoma. Systemic therapies such as corticosteroids and azathioprine are immunosuppressive and immunomodulatory and could facilitate malignant transformation .
Necrobiosis lipoidica is a chronic degenerative disease of dermal connective tissue, of unknown etiology, which occurs mostly in diabetic patients. The disease is cosmetically disfiguring and is associated with significant morbidity. The occurrence of complications such as ulceration and squamous cell carcinoma highlights the importance of understanding the pathogenesis of NL. Effective primary prevention strategies and new treatment options are needed to adequately control the disease and its progression.
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