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Ataxia-telangiectasia (Louis-Bar syndrome) associated with ulcerating necrobiosis lipoidica
124 Brief communications
Journal of the American Academy of Dermatology July 1994
Ataxia-telangiectasia (Louis-Bar syndrome) associated with ulcerating necrobiosis Iipoidica Anneliese Gotz, MD, Fritjof Eckert, MD, and Michael Landthaler, MD
Regensburg, Germany Louis-Bar syndrome was originally described by Louis-Bar in 1941. 1 On the basis of its most salient features, Boder and Sedgwick/ termed this condition ataxia-telangiectasia. Associated endocrinologic abnormalities often include diabetes. Schalch et al. 3 reported that 10 of 17 patients with ataxia-telangiectasia had hyperglycemia, and 9 of the 17 patients of McFarlin et a1. 4 were glucose intolerant. Necrobiosis lipoidica is closely linked to diabetes mellitus. 5-7 In most studies about 65% ofthe patients have diabetes and many others demonstrate abnormal glucose tolerance or have a family history of glucose intolerance.! To our knowledge the association of ataxia-telangiectasia with necrobiosis lipoidica has not been previously reported. CASE REPORT A developmentallydelayed l S-year-old girl was unable to walk without assistance. Seven years ago the findings of a clumsy, unsteady gait and telangiectases of the bulbar conjunctivae confirmed the diagnosis of ataxia-telangiectasia. She had progressive cerebellar ataxia and recurrent episodesofbronchopuImonary infection.Symptomless cutaneous lesions were first noted 2 years ago. Examination revealed bilateral medial and lateral bulbar conjunctival telangiectases (Fig. 1) and fine telangiectases across her nasal bridge and in periorbital skin and the butterfly area of the cheeks, the right ear, the upper part of the trunk, antecubital fossae, and neck. Mottled hyperpigmentation was present on the face. The right cheek had a hyperpigmented, irregular macule. A yellowbrown, atrophic plaque with superficialtelangiectases and a central ulcer was present onthe dorsal aspect of the right forearm and the right hand (Fig. 2). In addition, on the backofthe right hand and on the lateral aspect of the right thigh, irregular, indurated plaques with a central crust From the Department of Dermatology, University of Regensburg. Reprint requests: Anneliese Glitz, MD, Department of Dermatology, University of Regensburg, P.O. Box 10 06 62, D-93042 Regensburg, Germany. JAM ACAD DERMATOL 1994;31:124-6.
Copyright @ 1994 by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00
+ 16/54/52914
were noted. A biopsy specimen showed large, confluent palisadingnecrobioticgranulomas in the dermis with extensive ulceration of the overlying epidermis, confirming the diagnosis of necrobiosis lipoidica. The resultof an oral glucose tolerance test was negative, but the patient had increased fastening plasma insulin and C peptide levels. IgA was absent, IgM level was increased. There was a significant decrease in IgG2 and IgG4 levels, but total IgG levelwas normal. Evaluation of the cellular immune status indicateda significantincreasein CD8-positivecytotoxic T cellsand an increase of CD3jDR-activated T cells. Results of intradermal skin tests were negative, indicating an anergic state. Roentgenograms of the chest and the paranasal sinuses demonstrated signs of chronic recurrent pulmonary infections and sinusitis. A computed tomographic scan of the brain showed progressed cerebellar atrophy characterized by dysraphic components and a mild central cortical, mainly temporal, atrophy. DISCUSSION Ataxia-telangiectasia is a rare neurocutaneous and immunologic autosomal-recessive inherited disease with variable penetrance.?"! Its cardinal features are progressive cerebellar ataxia, oculocutaneous telangiectases, and recurrent respiratory infections because of disturbances ofboth the cellular and humoral immune system. No specific treatment is available. Our patient had ulcerating necrobiosis lipoidica. Necrobiosis lipoidica is closely linked to diabetes mellitus.l? Its development usually follows the onset of diabetes, develops simultaneously, or sometimes precedes glucose intolerance or the onset of overt diabetes by an average of 3 to 4 years. 13 Patients with necrobiosis lipoidica and normal glucose tolerance are thought to be in a prediabetic phase. Abnormal carbohydrate metabolism ranging from glucose intolerance to insulin-resistant diabetes mellitus has been associated with ataxia-telangiectasia.vf- 14 In patients with ataxia-telangiectasia, insulin-resistant diabetes is characterized by abnormal glucose tolerance, an elevated fasting plasma insulin level, and an excessive insulin production response to glucose or
Journal of the American Academy of Dermatology Volume 31, Number 1
Briefcom m unications 125
Fig. 1. Characteristic conjunctival telangiectases.
Fig. 2. Ulcerated lesions of necrobiosis lipoidica on back of hand and on dorsal aspect of forearm.
tolbutamide, but glucosuria and diabetic ketoacidosis are rare. Our patient had no evidence of diabetes or abnormal glucose tolerance. However, an increased fastening plasma insulin level was demonstrated. The necrobiosis lipoidica lesions were ulcerated and demonstrated the histologic pattern of palisading granulomas. Both ulceration and palisading granulomas in contrast to the tuberculoid type are thought to be more frequent in diabetic than in nondiabetic patients. 15The legs,especially the shins, are the most commonly affected sites of diabetes-associated necrobiosis. Extracrural involvement has been documented in only approximately 15%of all cases. Our patient's lesions, however, were present on the forearm, the hand, and the thigh, a finding that occurs
in fewer than 2% of patients with necrobiosis lipoidica. 13, 16 REFERENCES I. Louis-Bar D. Sur un syndrome progressif comprenant des telangiectasies capillaires cutanees et conjunctivales symetriques a disposition nevoide et des troubles cerebelleux, Conlin NeuroI1941;4:32-42. 2. Boder E, Sedgwick RP. Ataxia telangiectasia: a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasias and frequent pulmonary infections. Pediatrics 1958;21:525-56. 3. Schalch DS, McFarlin DE, Barlow MR. An unusual form of diabetes mellitus in ataxia-telangiectasia. N Engl J Med 1970;282:1396-402. 4. McFarlin DE, Strober W, Waldmann TA. Ataxia-telangiectasia. Medicine 1972;51:281-314 . 5. Lowitt MR, Dover JS. Necrobiosis lipoidica. JAM ACAD DERMATOL 1991;25:735-48.
126
Briefcommunications
6. Oppenheim M. Eigentiimliche disseminierte Degeneration des Bindegewebes der Haut bei einem Diabetiker [Letter]. Z Hautkr 1929-1930;32:179. 7. Urbach E. Beitrage zu einer physiologischen und pathologischen Chemie der Haut: eine neue diabetische Stoffwechseldermatose; Necrobiosis lipoidica diabeticorum [Letter]. Arch Dermatol Syph 1932;166:273. 8. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum: results of glucose-tolerance test in non-diabetic patients. JAMA 1966;195:433-66. 9. Cohen LE, Tanner DJ, Schaefer HG, et al. Common and uncommon cutaneous findings in patients with ataxiatelangiectasia. J AM ACAD DERMATOL 1984;10:431-8. 10. Peterson RDA, Funkouser JD. Ataxia telangietasia: an important clue. N Eng! J Moo 1990;322:124-5.
Journ al of the American Academy of Dermatology July 1994
11. Smith LS, Conerly SI. Ataxia-telangiectasia or Louis-Bar syndrome. JAM ACAD DERMATOL 1985;12:681-96. 12. Huntley AC. The cutaneous manifestations of diabetes mellitus. JAM ACAD DERMATOL 1982;7:427-55. 13. Smith JO . Necrobiosis lipoidica: a disease of changing concepts. Arch DermatoI1956;74:280-5. 14. Bar RS , Levis WR, Rechler MM, et al. Extreme insulin resistance in ataxia telangiectasia. N Engl J Moo 1978;298:1164-71. IS. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum: histopathologicstudy of 98 cases. Arch Dermatol 1966;94:1-10. 16. Lever WF, Schaumburg-Lever O. Necrobiosis lipoidica. In: Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:260-3.
Journal of the American Academy of Dermatology July 1994
Ataxia-telangiectasia (Louis-Bar syndrome) associated with ulcerating necrobiosis Iipoidica Anneliese Gotz, MD, Fritjof Eckert, MD, and Michael Landthaler, MD
Regensburg, Germany Louis-Bar syndrome was originally described by Louis-Bar in 1941. 1 On the basis of its most salient features, Boder and Sedgwick/ termed this condition ataxia-telangiectasia. Associated endocrinologic abnormalities often include diabetes. Schalch et al. 3 reported that 10 of 17 patients with ataxia-telangiectasia had hyperglycemia, and 9 of the 17 patients of McFarlin et a1. 4 were glucose intolerant. Necrobiosis lipoidica is closely linked to diabetes mellitus. 5-7 In most studies about 65% ofthe patients have diabetes and many others demonstrate abnormal glucose tolerance or have a family history of glucose intolerance.! To our knowledge the association of ataxia-telangiectasia with necrobiosis lipoidica has not been previously reported. CASE REPORT A developmentallydelayed l S-year-old girl was unable to walk without assistance. Seven years ago the findings of a clumsy, unsteady gait and telangiectases of the bulbar conjunctivae confirmed the diagnosis of ataxia-telangiectasia. She had progressive cerebellar ataxia and recurrent episodesofbronchopuImonary infection.Symptomless cutaneous lesions were first noted 2 years ago. Examination revealed bilateral medial and lateral bulbar conjunctival telangiectases (Fig. 1) and fine telangiectases across her nasal bridge and in periorbital skin and the butterfly area of the cheeks, the right ear, the upper part of the trunk, antecubital fossae, and neck. Mottled hyperpigmentation was present on the face. The right cheek had a hyperpigmented, irregular macule. A yellowbrown, atrophic plaque with superficialtelangiectases and a central ulcer was present onthe dorsal aspect of the right forearm and the right hand (Fig. 2). In addition, on the backofthe right hand and on the lateral aspect of the right thigh, irregular, indurated plaques with a central crust From the Department of Dermatology, University of Regensburg. Reprint requests: Anneliese Glitz, MD, Department of Dermatology, University of Regensburg, P.O. Box 10 06 62, D-93042 Regensburg, Germany. JAM ACAD DERMATOL 1994;31:124-6.
Copyright @ 1994 by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00
+ 16/54/52914
were noted. A biopsy specimen showed large, confluent palisadingnecrobioticgranulomas in the dermis with extensive ulceration of the overlying epidermis, confirming the diagnosis of necrobiosis lipoidica. The resultof an oral glucose tolerance test was negative, but the patient had increased fastening plasma insulin and C peptide levels. IgA was absent, IgM level was increased. There was a significant decrease in IgG2 and IgG4 levels, but total IgG levelwas normal. Evaluation of the cellular immune status indicateda significantincreasein CD8-positivecytotoxic T cellsand an increase of CD3jDR-activated T cells. Results of intradermal skin tests were negative, indicating an anergic state. Roentgenograms of the chest and the paranasal sinuses demonstrated signs of chronic recurrent pulmonary infections and sinusitis. A computed tomographic scan of the brain showed progressed cerebellar atrophy characterized by dysraphic components and a mild central cortical, mainly temporal, atrophy. DISCUSSION Ataxia-telangiectasia is a rare neurocutaneous and immunologic autosomal-recessive inherited disease with variable penetrance.?"! Its cardinal features are progressive cerebellar ataxia, oculocutaneous telangiectases, and recurrent respiratory infections because of disturbances ofboth the cellular and humoral immune system. No specific treatment is available. Our patient had ulcerating necrobiosis lipoidica. Necrobiosis lipoidica is closely linked to diabetes mellitus.l? Its development usually follows the onset of diabetes, develops simultaneously, or sometimes precedes glucose intolerance or the onset of overt diabetes by an average of 3 to 4 years. 13 Patients with necrobiosis lipoidica and normal glucose tolerance are thought to be in a prediabetic phase. Abnormal carbohydrate metabolism ranging from glucose intolerance to insulin-resistant diabetes mellitus has been associated with ataxia-telangiectasia.vf- 14 In patients with ataxia-telangiectasia, insulin-resistant diabetes is characterized by abnormal glucose tolerance, an elevated fasting plasma insulin level, and an excessive insulin production response to glucose or
Journal of the American Academy of Dermatology Volume 31, Number 1
Briefcom m unications 125
Fig. 1. Characteristic conjunctival telangiectases.
Fig. 2. Ulcerated lesions of necrobiosis lipoidica on back of hand and on dorsal aspect of forearm.
tolbutamide, but glucosuria and diabetic ketoacidosis are rare. Our patient had no evidence of diabetes or abnormal glucose tolerance. However, an increased fastening plasma insulin level was demonstrated. The necrobiosis lipoidica lesions were ulcerated and demonstrated the histologic pattern of palisading granulomas. Both ulceration and palisading granulomas in contrast to the tuberculoid type are thought to be more frequent in diabetic than in nondiabetic patients. 15The legs,especially the shins, are the most commonly affected sites of diabetes-associated necrobiosis. Extracrural involvement has been documented in only approximately 15%of all cases. Our patient's lesions, however, were present on the forearm, the hand, and the thigh, a finding that occurs
in fewer than 2% of patients with necrobiosis lipoidica. 13, 16 REFERENCES I. Louis-Bar D. Sur un syndrome progressif comprenant des telangiectasies capillaires cutanees et conjunctivales symetriques a disposition nevoide et des troubles cerebelleux, Conlin NeuroI1941;4:32-42. 2. Boder E, Sedgwick RP. Ataxia telangiectasia: a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasias and frequent pulmonary infections. Pediatrics 1958;21:525-56. 3. Schalch DS, McFarlin DE, Barlow MR. An unusual form of diabetes mellitus in ataxia-telangiectasia. N Engl J Med 1970;282:1396-402. 4. McFarlin DE, Strober W, Waldmann TA. Ataxia-telangiectasia. Medicine 1972;51:281-314 . 5. Lowitt MR, Dover JS. Necrobiosis lipoidica. JAM ACAD DERMATOL 1991;25:735-48.
126
Briefcommunications
6. Oppenheim M. Eigentiimliche disseminierte Degeneration des Bindegewebes der Haut bei einem Diabetiker [Letter]. Z Hautkr 1929-1930;32:179. 7. Urbach E. Beitrage zu einer physiologischen und pathologischen Chemie der Haut: eine neue diabetische Stoffwechseldermatose; Necrobiosis lipoidica diabeticorum [Letter]. Arch Dermatol Syph 1932;166:273. 8. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum: results of glucose-tolerance test in non-diabetic patients. JAMA 1966;195:433-66. 9. Cohen LE, Tanner DJ, Schaefer HG, et al. Common and uncommon cutaneous findings in patients with ataxiatelangiectasia. J AM ACAD DERMATOL 1984;10:431-8. 10. Peterson RDA, Funkouser JD. Ataxia telangietasia: an important clue. N Eng! J Moo 1990;322:124-5.
Journ al of the American Academy of Dermatology July 1994
11. Smith LS, Conerly SI. Ataxia-telangiectasia or Louis-Bar syndrome. JAM ACAD DERMATOL 1985;12:681-96. 12. Huntley AC. The cutaneous manifestations of diabetes mellitus. JAM ACAD DERMATOL 1982;7:427-55. 13. Smith JO . Necrobiosis lipoidica: a disease of changing concepts. Arch DermatoI1956;74:280-5. 14. Bar RS , Levis WR, Rechler MM, et al. Extreme insulin resistance in ataxia telangiectasia. N Engl J Moo 1978;298:1164-71. IS. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum: histopathologicstudy of 98 cases. Arch Dermatol 1966;94:1-10. 16. Lever WF, Schaumburg-Lever O. Necrobiosis lipoidica. In: Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:260-3.