Australas J. Dermatol 1992; 33: 31-34

FAMILIAL NON-DIABETIC NECROBIOSIS LIPOIDICA KENNETH K-L HO, S. O'LOUGHLIN AND F.C. POWELL

Dublin SUMMARY

Necrobiosis lipoidica (NL) is a cutaneous disorder with distinctive clinical and morphologic characteristics. It is associated with diabetes mellitus in two thirds of cases. The aetiology and pathogenesis ofNL are unknown but familial cases ofNL seem to be extremely rare. We report the occurrence of NL in two sisters with normal glucose tolerance. Key words: necrobiosis lipoidica, familial occurrence, aetiology, pathogenesis. ment of NL in close relatives suggests that genetic factors may play a role in the pathogenesis of NL.

INTRODUCTION

Necrobiosis lipoidica (NL) is a cutaneous disorder with lesions consisting of sharply defined plaques which have an atophic, telangiectatic, yellow brown centre, and an indurated, purple periphery. Ulceration may occur in one third of these lesions.' NL lesions are most frequently found bilaterally in the pretibial areas of the lower extremities, and may be associated with lesions occurring on the abdomen, upper extremities, face and scalp in 15% of patients.' Most cases of NL (80%)' affect females. Although NL is only found in 0.3% of diabetic patients; two thirds of patients with NL suffer from diabetes mellitus' with diabetes being a concomitant finding in 86 to 93% of these patients at the onset of NL lesions.'^ Most reported cases of diabetes associated with NL were insulin dependent and of early onset (type 1).'^ The aetiology of NL is unknown. Collagen degeneration is widely regarded as the primary event in its pathogenesis^ while some argue that vasculopathy may be important in the initiation of necrobiosis.'' The ocurence of NL in a family setting seem to be extremely rare and, to our knowledge, only two pairs of siblings with NL have been documented in one report.' Here, we report NL lesions in two sisters with normal glucose tolerance. Develop-

CASE REPORTS

A 48 year old female patient presented to the Regional Centre of Dermatology (Dublin) with asymptomatic erythematous oval lesions affecting both shins which had been present for two years. The lesions commenced as red circles, and they had been gradually extending on the skin surface. Her younger sister (aged 47 years) also

Kenneth K-L Ho, BMedSc, MBBS. Fellow in Dermatology. S. O'Loughlin, FRCPl. Consultant Dermatologist. F.C. Powell, FRCPI. Consultant Dermatologist. The Regional Centre of Dermatology, Mater Misericordiae Hospital, Dublin. Address for correspondence: Dr F.C. Powell, The Regional Centre of Dermatology, Mater Misericordiae Hospital, Eccles St, Dublin, Ireland. Dr K Ho is in receipt of the Janssen-Cilag Travelling Scholarship of the Australian College of Dermatologists to the Regional Centre of Dermatology (Dublin).

FIGURE 1—NL lesions of the patient.

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KENNETH K-L HO, S. O'LOUGHLIN AND EC. POWELL

had similar lesions on both shins, which started at the age of 39 years and were complicated by ulcerations five years later. Her older brother (aged 50 years) suffered from obesity and noninsulin dependent diabetes mellitus diagnosed at the age of 41 years (type II diabetes), but he had no skin complaints. Our patient had a history of carcinoma in the right breast which had been treated surgically 14 years previously. On examination, oval shaped, sharply demarcated, atrophic patches with a brownish yellow centre traversed by telangiectases and an erythematous brown margin were found in the pretibial area of both legs (Fig 1). The leson in the right leg measured 22 x 11 mm. Two similar but smaller patches were located on the left lower leg. Ulceration was absent. Similar but much larger lesions complicated by ulceration were found in the patient's sister in the same areas (Fig 2). Skin biopsy showed the presence of palisading granulomas occupying the entire thickness of the dermis (Fig 3). Skin biopsy from the sister's lesions revealed disordered and partially degenerate collagen bundles in the dermis infiltrated by lymphocytes and histiocytes (Fig 4). Epithelioid cells and giant cells were present in abundance. These features were consistent with necrobiosis lipoidica in both biopsies. Standard glucose tolerance tests for both sisters were normal. The asymptomatic lesions were treated with emollients in our patient, and ulcerated lesions were treated with silver sulphadiazine dressings, with slow improvement. DISCUSSION

The familial occurrence of necrobiosis lipoidica is rare. No familial cases were reported in a series of 171 patients with NL.' Findlay et al^ reported the occurrence of familial NL in 2 brothers with onset of lesions at the age of 22 years in both patients, and a separate familial case involving a brother and a sister with onset of lesions at 19 and 22 years of age respectively. None of their patients had a history of diabetes and three of them were investigated and found to have normal glucose tolerance tests. It is interesting to note that, despite a positive family history of type II diabetes, both our patient and her sister had normal glucose tolerance. The risk of developing diabetes in these patients with NL is likely to be higher than the general population. In the series

FiGLiRE 2—NL lesions of the patient's sister, showing more extensive involvement with areas of ulceration.

reported by MuUer and Winkelmann,' 42% of 19 patients with NL but not history of diabetes showed abnormal glucose tolerance either concurrently or prospectively with the onset of NL lesions. Seviour and Elkeles subsequently reported the occurrence of NL in two HLAmatched diabetic sisters." The aetiology of NL is unknown. Collagen degeneration is a prominent and constant feature of NL lesions both histologically and ultrastructurally.' In addition, the concentration of collagen has been shown to be markedly decreased in lesional skin.' Fibroblasts isolated from affected skin have been found to synthesize less collagen than those from the uninvolved areas. The collagen defect within NL lesions may thus be both qualitative and quantitative. It has been postulated that the histologic features of NL lesions reflect a cell mediated immune reaction against the altered collagen fibres.' This is further supported by the recent finding that the number of epidermal Langerhans cells, antigen presenting cells essential for the initiation of cell mediated immune reactions, was increased in the lesional areas.' Knowledge of the changes leading to

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FAMILIAL NON-DIABETIC NECROBIOSIS LIPOIDICA

FIGURE 3—Photomicrograph of the NL lesion from the patient, showing areas of necrobiosis infiltrated by large foci of lymphocytes, histiocytes and multi-nucleate giant cells in a palisading pattern. (H&E x 10)

FIGURE 4—Photomicrograph of the NL lesion from Ihc palicnt's sister, showing necrobiosis with a more diffuse infiltration of lymphocytes, histiocytes and multi-nucleate giant cells. (H&E x 10) 33

KENNETH K-L HO, S. O'LOUGHLIN AND F.C. POWELL

collagen degeneration is incomplete. Intralesional vasculopathic changes with perivascular depositions of IgM, IgG or IgA, fibrin and C3, as found in some lesions,'" may imply that an immune mediated vasculitis could be responsible. However, this is unlikely to be the primary pathogenic change in all cases, as vascular changes are absent in one third of NL lesions." Familial cases of NL, as reported here, suggest that genetic predisposition may be another important pathogenic factor. Finally, it is interesting to note that familial cases of granuloma annulare, a disorder which may occur in association with'^ and share many histologic features of NL,' have also been reported.'^

REFERENCES Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum - a clinical and pathological investigation of 171 cases. Arch Dermatol 1966; 93: 272-81. Boulton AJM, Cutfield RG, Abouganem D, et al. Necrobiosis lipoidica diabeticorum: a clinicopathologic study. J Am Acad Dermatol 1988; 18: 530-7.

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Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia, JB Lippincott Company. 1990; 260-3. Dahl M. Immunofluroescence, necrobiosis lipoidica, and blood vessels. Arch Dermatol 1988; 124: 1417-9. Findlay GH, Morrison JGL, De Beer HA. Non-diabetic necrobiosis lipoidica. S Afr Med J 1981; 59: 323-6. Seviour PW, Elkeles RS. Necrobiosis lipoidica in two diabetic sisters. Clin Exp Dermatol 1985; 10: 159-61. Oikarinen A, Mortenhumer M, Kallioinen M, Savolainen E-R. Necrobiosis lipoidica: ultrastructural and biochemical demonstration of a collagen defect. J Invest Dermatol 1987; 88: 27-32. Wood MG, Beerman H. Necrobiosis lipoidica, granuloma annulare, and rheumatoid nodule. J Invest Dermatol I960; 34: 139-47. Chambers B, Milligan A, Fletcher A. Epidermal dendritic SlOO positive cells in necrobiosis lipoidica and granuloma annulare. Br J Dermatol 1990; 123: 765-8. Quimby SR, Muller SR, Schroeter AL. The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. Arch Dermatol 1988; 124: 1364-71. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum - histopathologic study of 98 cases. Arch Dermatol 1966; 94: 1-10. Cohen UK. Necrobiosis lipoidica and granuloma annulare. J Am Acad Dermatol 1894; 10: 123-4. Abrusci V, Weiss E, Planas G. Familial generalized perforating granuloma annulare. Int J Dermatol 1988; 27: 126-7.

Familial non-diabetic necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a cutaneous disorder with distinctive clinical and morphologic characteristics. It is associated with diabetes mellitus ...
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