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Absence of antiphospholipid and anti-endothelial cell antibodies in malignant atrophic papulosis: A study of 15 cases
Journal of the American Academy of Dermatology Volume 33, Number 5, Part 1
Brief communications
831
Absence of antiphospholipid and anti-endothelial cell antibodies in malignant atrophic papulosis: A study of 15 cases H. Assier, MD,a*d 0. Chosidow, MD,” J. C. Piette, MD: M. C. Boffa, MD, PhD,b P. Youinou, MD, PhD,’ L. Thomas, MD,d F. Caux, MD,d B. Cribier, MD,d J. M. Bonnet-Blanc, MD,d G. Guillet, MD,d P. Plantin, MD,d R. Triller, MD,d A. Cosnes, MD,d E. Delaporte, MD,d M. Dandurand, MD,d and C. Fran&s, MD Paris and Brest, France Malignant atrophic papulosis is a rare but often lethal disease characterized by thrombotic vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and occasionally other organs. ‘72 Its pathogenesis is unknown. Hypercoagulopathy or endothelial cell pathology have frequently been postulated without fin-ther confirmation.3-7 Because one case of malignant atrophic papulosis associated with antiphospholipid antibodies was reported 10 years ago,8 we decided to determine the prevalence of antiphospholipid antibodies and antiendothelial cell antibodies (AECA) in a large series of patients with malignant atrophic papulosis. MATERIAL
Fig. 1. Typical porcelain white--centered papules with telangiectatic rims on the trunk.
AND METHODS
A prospective multicenter national study was conducted between September 1992 and March 1994 in French dermatology departments. All patients with a
clinical diagnosis of malignant atrophic papulosis were included. This clinical diagnosis was based on the presence of several skin papules with central porcelain-white atrophy and a telangiectatic border (Fig. 1). The following clinical and biologic data were recorded: patient’s age at the time of the diagnosis, number of papules, systemic involvement, routine coagulation, and fibrinolysis tests. Blood samples were collected for detection of antiphospholid antibodies and AECA, sera and plasma were stored at -70” C until assayed. Lupus anticoagulant was detected by activated partial thromboplastin and kaolin clotting time tests using commercially available reagents. From the Department of Internal Medicine, HSpital de la Piti&Sal$tr&e, Parka; Hbpital Saint-Louis,Parisb; Laboratoired’hnmunologie, CHU de Brestc; and the National Cooperative Group for the Study of Malignant Atrophic Papulosis.d Reprint requests: Camille Franc&s, MD, Groupe Hospitalier PitiC-%$&i&e, 75651 Paris Cedex 13, France. J AM ACAD DF.RMATOL Copyright 0190.9622/X
1995;33:831-3.
0 1995 by the American $5.00 + 0
Service de M&k&e Inteme, 83, boulevard de l’Hapital,
Academy
16/54/66415
of Dermatology,
Inc.
Fig. 2. Triangular dermal necrosis underneath an atrophic epidermis. Antibodies to cardiolipin, mixed anionic phospholipids (cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol) and phosphatidyl-ethanolamine (lame&r phase) were measured by enzyme-linked immunosorbent assays (ELISA) with phospholipids from lipid products (South Nutfield, U.K.) as previously described.9 AECA were detected in an ELISA using hybrid cells EA.hy926 provided by C. J. Edgell (Chapel Hill, N.C.).” The line had been established by fusing human umbilical
Journal
of the American
Academy
832 Brief communications
of Dermatology November 1995
Table I. Clinical data on 15 patients with malignant atrophic papulosis Organ Patient No.
Sex
1
M
2 3 4 5 6 7 8 9
F M M F M F F F
10 11
M
12 13 14 15 *Age
F F M F F
Age* W1
No. of papd=
Gut
Eye
35 68 62 30 34 36 27
15 >lOO >lKl
+ +
+ +
5 35 75 15
+ + + +
+
13
10 >loo
+
35
+
31 47 26 56 34 66 18
>loo
+
+
involvement
Brain
Lung
+
+
+
+
Kidney
+
Heart
+
+
15 75 15 5
at the time of diagnosis.
vein endothelial cells with the permanent human cell line (A 549/8) derived from a lung carcinoma. The sera were tested before and after adsorption on epithelial cells (A 549/8) to avoid false-positivity from membranous epithelial antigens on the hybrid cells.ri Results were considered positive when titers were higher than 3 standard deviations above the mean of controls. RESULTS Fifteen patients, 9 women and 6 men, whose mean age at the time of diagnosis was 39 years (range, 13 to 68 years), were included in the study. Their clinical data are reported in Table I. The number of papules varied from 5 to more than 100. Intestinal lesions, present in nine patients, were sometimes associated with lesions of the eye (four cases), brain (two) lung (two), heart (two), and/or kidney (one), Three patients had prolonged euglobulin lysis times, four had increased serum fibrinogen levels, and one had increased platelet adhesiveness. None of the patients had any antiphospholipid antibodies of any type or P&CA. DISCUSSION The pathogenesis of malignant atrophic papulosis is still a subject of debate. Histologic examination shows a definite area of dermal necrosis just below an atrophic epidermis (Fig. 2). Vascular damage predominates in the arterioles, but veins, venules, and small arteries may also be affected. Blood vessel occlusion is associated with endothelial cell
swelling and a sparse and patchy perivascular lymphocyte infiltrate.2 Because there is little inflammation of the vessel wall, malignant atrophic papulosis was thought to be a hypercoagulation syndrome with inhibited fibrinolysis. This hypothesis was supported by all the different abnormalities that were described more or less individually in isolated case reports. These include increased serum fibrinogen level, perivascular fibrinogen deposits, consumption coagulopathy, cryofibrinogen, cryoglobulin, decreased local fibrinolytic activity, prolonged euglobulin lysis time, increased adhesiveness and aggregation of platelets, and increased plasminogen activator.3-71 12-t5 Similarly, antiphospholipid antibodies were observed in only one patient with malignant atrophic papulosis and were absent in three others.“? r5-17 Laboratory tests for syphilis with long-term false-positive results have never been reported. Our results concerning the largest series of patients with malignant atrophic papulosis confirm the absence of a relation between malignant atrophic papulosis and antiphospholipid antibodies. The only reported patient with malignant atrophic papulosis and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) had ischemic myelopathy and occlusion of the central retinal artery without intestinal lesions.8 These neurologic manifestations are more frequently encountered in antiphospholipid syndrome than in malignant atrophic papul0sis.l’ Therefore this patient might have had antiphospholipid syndrome
Journal of the American Academy of Dermatology Volume 33, Number 5, Part 1
with atrophie blanche lesions closely resembling those of malignant atrophic papulosis. Similar skin lesions have been described in primary antiphosphohpid syndrome and antiphospholipid syndrome associated with systemic lupus erythematosus.1g-22 The endothelial damage of vessels observed in malignant atrophic papulosis led us to look for AECA in this disease. AECA were previously detected in a wide variety of clinical settings, especially in antiphospholipid syndrome and systemic vasculiti~.~~~~~Their absence in malignant atrophic papulosis does not support the involvement of an autoimmune mechanism in the pathogenesis of this disease. Moreover, this last theory was previously considered to be unlikely because of the absence of true vasculitis and of immunologic abnormalities, especiahy circulating immune complexes.26 The recent ultrastructural demonstration of an increased number of Weibel-Paladc bodies and a more intense staining of von Willebrand factor in endothehal cells suggests a primary endothelial defect.” The absence of antiphospholipid antibodies and AEEA in this large series of patients with malignant atrophic papulosis suggests that another mechanism is involved in this often lethal disease. Reports of familial cases of malignant atrophic papulosis emphasize the possibility of genetic factors,283 2g thereby providing a lead that remains to be explored. REFERENCES 1. Kohhneier W. Multiple hautnekrosen bei thrombangiitis obliterans. Arch Dermatol Syphilol 1941;181:783-92. 2. Degos R. Malignant atrophic papulosis. Br J Dermatol 1979; 100:21-35. 3. Daniel F, Foix C, Gray J-M, et al. Papulose atrophiante maligne avec insuffisance de la fibrinolyse sanguine. Ann Dermatol Venereol 1982;109:763-4. 4. Black MM, Nishioka K, Levene GM. The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Degas’ disease). Br J Dermatol 1973;88:212-9. 5. Howsden SM, Hodge SJ, Hemdon JH, et al. Malignant atrophic papulosis of Degos: report of a patient who failed to respond to fibrinolytic therapy. Arch Dermatol 1976; 112:1582-g. 6. Stahl D, Thomsen K, Hou-Jensen K. Malignant atrophic papulosis: treatment with aspirin and dipyridamole. Arch Dermatol 1978;114:1687-9. 7. Datsur DK, Singhal BS, Shroff HJ. CNS involvement in malignant atrophic papulosis (Kohhneier-Degos disease): vasculopathy and coagulopathy. J Neurol Neurosurg Psychiatry 1981;41:156-60. 8. Englert HJ, Hawkes CH, Boey ML, et al. Degos’ disease: association with anticardiolipin antibodies and the lupus anticoagulant @et&]. Br Med J 1984;289:576.
Brief communications 833 9. Karmochkine M, Berard M, Piette JC, et al. Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus. Lupus 1993;2:157-60. 10. Edgell CJS, McDonald CC, Graham JB. Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 1983; 80:3734-7. 11. Heurkens AHM, Gorter A, de Vreede TM, et al. Methods for the detection of anti-endothelial antibodies by enzymelinked immunosorbent assay. J Immunol Methods 1991; 141:33-9. 12. Drucker CR. Malignant atrophic papulosis: response to antiplatelet therapy. Dermatologica 1990;180:90-2. 13. Paramo JA, Rocha E, Cuesta B, et al. Fibrinolysis in Degos’ disease [Letter]. Thromb Haemost 1985;54:780. 14. Roenigk HH, Farmer RG. Degos’ disease (malignant papulosis). JAMA 1968;206:1508-14. 15. Bulengo-Ransby SM, Bums MK, Taylor WB, et al. Peristomal atrophic papules. Arch Dermatol 1992;128:256-7, 259-60. 16. Den&u T, Nakajima K, Oknyama R, et al. Malignant atrophic papulosis @egos’ syndrome). Int J Dermatol 1992;31:99-102. 17. Burrow JN, Iyer PV, Blumbergs PC, et al. KohhneierDegos disease: a multisystem vasculopathy with progressive cerebral infarction. Aust N Z J Med 1991;21:49-51. 18. Subbiah P, Wijdicks E, Carter J, et al. Degos’ disease: skin lesion with a fatal neurologic outcome. Neurology 1994; 44(suppl2):A251. 19. Alegre VA, Gastineau DA, Winkehnann RK. Skin lesions associated with circulating lupus anticoagulant. Br J Dermatol 1989;120:419-29. 20. Doutre MS, Beylot C, Bioulac P, et al. Skin lesion resembling malignant atrophic papulosis in lupus erythematosus. Dermatologica 1987;175:45-6. 21. Dublin HV, Stawiski MA. Systemic lupus erythematosus resembling malignant atrophic papulosis. Arch Intern Med 1974; 134:321-3. 22. Black MM, Hudson PM. Atrophic blanche lesions closely resembling malignant atrophic papulosis (Degas’ disease) in systemic lupus erythematosus. Br J Dermatol 1976; 95649-52. 23. McCrae KR, DeMichele A, Samuels P, et al. Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies. Br J Haematol 1991;79:595605. 24. Nylander-Lundqvist E, Back 0, Nilsson TK, et al. Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases. Clin Rheumatol 1992;11:248-53. 25. Adler Y, Salozhin K, Le Tonqueze M, et al. Antiendothelial cell antibodies: a need for standardization. Lupus 1994;3:77-84. 26. Tribble K, Archer ME, Jorizzo JL, et al. Malignant atrophic papulosis: absence of circulating immune complexes and vasxlitis. J AM ACAD DERMATOL 1986;15:365-9. 27. Caux F, Aractingi S, Scrobohaci ML, et al. Anomalies de la fibrinolyse dans la maladie de Degos: etude de 3 cas. Ann Dermatol Venereol 1994;121:537-42. 28. Moulin G, Barmt D, Franc MP, et al. Papulose atrophiante de Degos familiale (mere-fille). Ann Dermatol Venereol 1984; 111:149-55. 29. Kisch LS, Bmynzeel DP. Six cases of malignant atrophic papulosis @egos’s disease) occurring in one family. Br J Dermatol 1984; 111:469-7 1.
Brief communications
831
Absence of antiphospholipid and anti-endothelial cell antibodies in malignant atrophic papulosis: A study of 15 cases H. Assier, MD,a*d 0. Chosidow, MD,” J. C. Piette, MD: M. C. Boffa, MD, PhD,b P. Youinou, MD, PhD,’ L. Thomas, MD,d F. Caux, MD,d B. Cribier, MD,d J. M. Bonnet-Blanc, MD,d G. Guillet, MD,d P. Plantin, MD,d R. Triller, MD,d A. Cosnes, MD,d E. Delaporte, MD,d M. Dandurand, MD,d and C. Fran&s, MD Paris and Brest, France Malignant atrophic papulosis is a rare but often lethal disease characterized by thrombotic vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and occasionally other organs. ‘72 Its pathogenesis is unknown. Hypercoagulopathy or endothelial cell pathology have frequently been postulated without fin-ther confirmation.3-7 Because one case of malignant atrophic papulosis associated with antiphospholipid antibodies was reported 10 years ago,8 we decided to determine the prevalence of antiphospholipid antibodies and antiendothelial cell antibodies (AECA) in a large series of patients with malignant atrophic papulosis. MATERIAL
Fig. 1. Typical porcelain white--centered papules with telangiectatic rims on the trunk.
AND METHODS
A prospective multicenter national study was conducted between September 1992 and March 1994 in French dermatology departments. All patients with a
clinical diagnosis of malignant atrophic papulosis were included. This clinical diagnosis was based on the presence of several skin papules with central porcelain-white atrophy and a telangiectatic border (Fig. 1). The following clinical and biologic data were recorded: patient’s age at the time of the diagnosis, number of papules, systemic involvement, routine coagulation, and fibrinolysis tests. Blood samples were collected for detection of antiphospholid antibodies and AECA, sera and plasma were stored at -70” C until assayed. Lupus anticoagulant was detected by activated partial thromboplastin and kaolin clotting time tests using commercially available reagents. From the Department of Internal Medicine, HSpital de la Piti&Sal$tr&e, Parka; Hbpital Saint-Louis,Parisb; Laboratoired’hnmunologie, CHU de Brestc; and the National Cooperative Group for the Study of Malignant Atrophic Papulosis.d Reprint requests: Camille Franc&s, MD, Groupe Hospitalier PitiC-%$&i&e, 75651 Paris Cedex 13, France. J AM ACAD DF.RMATOL Copyright 0190.9622/X
1995;33:831-3.
0 1995 by the American $5.00 + 0
Service de M&k&e Inteme, 83, boulevard de l’Hapital,
Academy
16/54/66415
of Dermatology,
Inc.
Fig. 2. Triangular dermal necrosis underneath an atrophic epidermis. Antibodies to cardiolipin, mixed anionic phospholipids (cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol) and phosphatidyl-ethanolamine (lame&r phase) were measured by enzyme-linked immunosorbent assays (ELISA) with phospholipids from lipid products (South Nutfield, U.K.) as previously described.9 AECA were detected in an ELISA using hybrid cells EA.hy926 provided by C. J. Edgell (Chapel Hill, N.C.).” The line had been established by fusing human umbilical
Journal
of the American
Academy
832 Brief communications
of Dermatology November 1995
Table I. Clinical data on 15 patients with malignant atrophic papulosis Organ Patient No.
Sex
1
M
2 3 4 5 6 7 8 9
F M M F M F F F
10 11
M
12 13 14 15 *Age
F F M F F
Age* W1
No. of papd=
Gut
Eye
35 68 62 30 34 36 27
15 >lOO >lKl
+ +
+ +
5 35 75 15
+ + + +
+
13
10 >loo
+
35
+
31 47 26 56 34 66 18
>loo
+
+
involvement
Brain
Lung
+
+
+
+
Kidney
+
Heart
+
+
15 75 15 5
at the time of diagnosis.
vein endothelial cells with the permanent human cell line (A 549/8) derived from a lung carcinoma. The sera were tested before and after adsorption on epithelial cells (A 549/8) to avoid false-positivity from membranous epithelial antigens on the hybrid cells.ri Results were considered positive when titers were higher than 3 standard deviations above the mean of controls. RESULTS Fifteen patients, 9 women and 6 men, whose mean age at the time of diagnosis was 39 years (range, 13 to 68 years), were included in the study. Their clinical data are reported in Table I. The number of papules varied from 5 to more than 100. Intestinal lesions, present in nine patients, were sometimes associated with lesions of the eye (four cases), brain (two) lung (two), heart (two), and/or kidney (one), Three patients had prolonged euglobulin lysis times, four had increased serum fibrinogen levels, and one had increased platelet adhesiveness. None of the patients had any antiphospholipid antibodies of any type or P&CA. DISCUSSION The pathogenesis of malignant atrophic papulosis is still a subject of debate. Histologic examination shows a definite area of dermal necrosis just below an atrophic epidermis (Fig. 2). Vascular damage predominates in the arterioles, but veins, venules, and small arteries may also be affected. Blood vessel occlusion is associated with endothelial cell
swelling and a sparse and patchy perivascular lymphocyte infiltrate.2 Because there is little inflammation of the vessel wall, malignant atrophic papulosis was thought to be a hypercoagulation syndrome with inhibited fibrinolysis. This hypothesis was supported by all the different abnormalities that were described more or less individually in isolated case reports. These include increased serum fibrinogen level, perivascular fibrinogen deposits, consumption coagulopathy, cryofibrinogen, cryoglobulin, decreased local fibrinolytic activity, prolonged euglobulin lysis time, increased adhesiveness and aggregation of platelets, and increased plasminogen activator.3-71 12-t5 Similarly, antiphospholipid antibodies were observed in only one patient with malignant atrophic papulosis and were absent in three others.“? r5-17 Laboratory tests for syphilis with long-term false-positive results have never been reported. Our results concerning the largest series of patients with malignant atrophic papulosis confirm the absence of a relation between malignant atrophic papulosis and antiphospholipid antibodies. The only reported patient with malignant atrophic papulosis and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) had ischemic myelopathy and occlusion of the central retinal artery without intestinal lesions.8 These neurologic manifestations are more frequently encountered in antiphospholipid syndrome than in malignant atrophic papul0sis.l’ Therefore this patient might have had antiphospholipid syndrome
Journal of the American Academy of Dermatology Volume 33, Number 5, Part 1
with atrophie blanche lesions closely resembling those of malignant atrophic papulosis. Similar skin lesions have been described in primary antiphosphohpid syndrome and antiphospholipid syndrome associated with systemic lupus erythematosus.1g-22 The endothelial damage of vessels observed in malignant atrophic papulosis led us to look for AECA in this disease. AECA were previously detected in a wide variety of clinical settings, especially in antiphospholipid syndrome and systemic vasculiti~.~~~~~Their absence in malignant atrophic papulosis does not support the involvement of an autoimmune mechanism in the pathogenesis of this disease. Moreover, this last theory was previously considered to be unlikely because of the absence of true vasculitis and of immunologic abnormalities, especiahy circulating immune complexes.26 The recent ultrastructural demonstration of an increased number of Weibel-Paladc bodies and a more intense staining of von Willebrand factor in endothehal cells suggests a primary endothelial defect.” The absence of antiphospholipid antibodies and AEEA in this large series of patients with malignant atrophic papulosis suggests that another mechanism is involved in this often lethal disease. Reports of familial cases of malignant atrophic papulosis emphasize the possibility of genetic factors,283 2g thereby providing a lead that remains to be explored. REFERENCES 1. Kohhneier W. Multiple hautnekrosen bei thrombangiitis obliterans. Arch Dermatol Syphilol 1941;181:783-92. 2. Degos R. Malignant atrophic papulosis. Br J Dermatol 1979; 100:21-35. 3. Daniel F, Foix C, Gray J-M, et al. Papulose atrophiante maligne avec insuffisance de la fibrinolyse sanguine. Ann Dermatol Venereol 1982;109:763-4. 4. Black MM, Nishioka K, Levene GM. The role of dermal blood vessels in the pathogenesis of malignant atrophic papulosis (Degas’ disease). Br J Dermatol 1973;88:212-9. 5. Howsden SM, Hodge SJ, Hemdon JH, et al. Malignant atrophic papulosis of Degos: report of a patient who failed to respond to fibrinolytic therapy. Arch Dermatol 1976; 112:1582-g. 6. Stahl D, Thomsen K, Hou-Jensen K. Malignant atrophic papulosis: treatment with aspirin and dipyridamole. Arch Dermatol 1978;114:1687-9. 7. Datsur DK, Singhal BS, Shroff HJ. CNS involvement in malignant atrophic papulosis (Kohhneier-Degos disease): vasculopathy and coagulopathy. J Neurol Neurosurg Psychiatry 1981;41:156-60. 8. Englert HJ, Hawkes CH, Boey ML, et al. Degos’ disease: association with anticardiolipin antibodies and the lupus anticoagulant @et&]. Br Med J 1984;289:576.
Brief communications 833 9. Karmochkine M, Berard M, Piette JC, et al. Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus. Lupus 1993;2:157-60. 10. Edgell CJS, McDonald CC, Graham JB. Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 1983; 80:3734-7. 11. Heurkens AHM, Gorter A, de Vreede TM, et al. Methods for the detection of anti-endothelial antibodies by enzymelinked immunosorbent assay. J Immunol Methods 1991; 141:33-9. 12. Drucker CR. Malignant atrophic papulosis: response to antiplatelet therapy. Dermatologica 1990;180:90-2. 13. Paramo JA, Rocha E, Cuesta B, et al. Fibrinolysis in Degos’ disease [Letter]. Thromb Haemost 1985;54:780. 14. Roenigk HH, Farmer RG. Degos’ disease (malignant papulosis). JAMA 1968;206:1508-14. 15. Bulengo-Ransby SM, Bums MK, Taylor WB, et al. Peristomal atrophic papules. Arch Dermatol 1992;128:256-7, 259-60. 16. Den&u T, Nakajima K, Oknyama R, et al. Malignant atrophic papulosis @egos’ syndrome). Int J Dermatol 1992;31:99-102. 17. Burrow JN, Iyer PV, Blumbergs PC, et al. KohhneierDegos disease: a multisystem vasculopathy with progressive cerebral infarction. Aust N Z J Med 1991;21:49-51. 18. Subbiah P, Wijdicks E, Carter J, et al. Degos’ disease: skin lesion with a fatal neurologic outcome. Neurology 1994; 44(suppl2):A251. 19. Alegre VA, Gastineau DA, Winkehnann RK. Skin lesions associated with circulating lupus anticoagulant. Br J Dermatol 1989;120:419-29. 20. Doutre MS, Beylot C, Bioulac P, et al. Skin lesion resembling malignant atrophic papulosis in lupus erythematosus. Dermatologica 1987;175:45-6. 21. Dublin HV, Stawiski MA. Systemic lupus erythematosus resembling malignant atrophic papulosis. Arch Intern Med 1974; 134:321-3. 22. Black MM, Hudson PM. Atrophic blanche lesions closely resembling malignant atrophic papulosis (Degas’ disease) in systemic lupus erythematosus. Br J Dermatol 1976; 95649-52. 23. McCrae KR, DeMichele A, Samuels P, et al. Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies. Br J Haematol 1991;79:595605. 24. Nylander-Lundqvist E, Back 0, Nilsson TK, et al. Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases. Clin Rheumatol 1992;11:248-53. 25. Adler Y, Salozhin K, Le Tonqueze M, et al. Antiendothelial cell antibodies: a need for standardization. Lupus 1994;3:77-84. 26. Tribble K, Archer ME, Jorizzo JL, et al. Malignant atrophic papulosis: absence of circulating immune complexes and vasxlitis. J AM ACAD DERMATOL 1986;15:365-9. 27. Caux F, Aractingi S, Scrobohaci ML, et al. Anomalies de la fibrinolyse dans la maladie de Degos: etude de 3 cas. Ann Dermatol Venereol 1994;121:537-42. 28. Moulin G, Barmt D, Franc MP, et al. Papulose atrophiante de Degos familiale (mere-fille). Ann Dermatol Venereol 1984; 111:149-55. 29. Kisch LS, Bmynzeel DP. Six cases of malignant atrophic papulosis @egos’s disease) occurring in one family. Br J Dermatol 1984; 111:469-7 1.