Volume 22 Number 2, Part 2 February 1990
8.
9. 10. 11. 12. 13. 14.
the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE. Rheum Int 1985;5:91-3. Harris EN, Asherson RA, Gharavi AE, et al. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibodies. Br J Haematol 1985; 59:227-30. Hughes GRV. Connective tissue disease and the skin. Clin Exp Dermatol 1984;9:535-44. Conley CL, Hartman RC. A haemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952;31:621-2. Boxer M, Ellman L, Carvalho A. The lupus anticoagulant. Arthritis Rheum 1976;19:1244-8. Schleider MA, Nachman RL, Jaffee EA, et al. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. Harris EN, HughesGRV.Antiphospholipidantibodies. In: McCarty D J, ed. Arthritis and allied conditions. 1 lth ed. Philadelphia: Lea & Febiger (In press). Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobin MX coagulation inhibitor with phospholipid specificity: mechanism of a lupus anticoagulant. J Clin Invest 1980;66:397-405.
Cutaneous necrosis with eardiolipin antibodies 15. Carreras LO, Defreyn J, Machin SJ, et al. Arterial thrombosis, intrauterine death and lupus anticoagulant: detection of immunoglobulin interfering with prostacyclin formation. Lancet 1981;1:244-6. 16. Cosgriff TM, Martin BA. Low functional and high antigenic antithrombin III level in a patient with the lupus anticoagulant and recurrent thrombosis. Arthritis Rheum 1981 ;24:94-6. 17. Sanfelippo M J, Drayna CJ. Prekallikrein inhibition associated with the lupus anticoagulant: a mechanism of thrombosis. Am J Clin Pathol 1982;77:275-9. 18. Harris EN, Hughes GRV, Gharavi AE. Anticardiolipin antibodies and the lupus anticoagulant. Clin Exp Rheumatol 1986;4:187-90. 19. Dodd H J, Sarkany l, O'Shaughnessy D. Widespread cutaneous necrosis associated with the lupus anticoagulant. Clin Exp Dermatol 1985;10:581-6. 20. Johansson EA, Niemi KM, Mustakallio KK. A peripheral vascular syndrome overlapping with systemic lupus erythematosus. Dermatologica 1977;155:257-67. 21. Lockshin MD.Anticardiolipinantibodies [Editorial].Arthritis Rheum 1987;30:471-2.
Purpuric contact dermatitis to benzoyl peroxide T h e o d o o r van Joost, M D , a Jos~ van Ulsen, M D , a Voijislav D. Vuzevsld, M D , b B e r n a r d N a a f s , M D , a and B h u p e n d r a T a n k , P h D a Rotterdam, The Netherlands Patch test reactions in a patient with purpuric contact dermatitis to 5% benzoyl peroxide are described. Alterations of the capillary endothelium included obliteration of the lumina with perivascular mononuclear cell infiltrates. There were no epidermal alterations. These observations are discussed with reference to the data in the literature on vascular damage in "dermal" contact dermatitis. (J AM ACAO DERMATOL 1990;22:359-61.) W e report our light and electron microscopy observations in a patient with a persistent purpuric c~ dermatitis caused by a d r u g containing benzoyl peroxide.
CASE R E P O R T An acute nonpruritic eruption characterized by infiltrated erythematous papules with focal purpura developed on the cheeks and the chin of a 22-year-old Asian From tile Departments of Dermato-Venereologya and Clinical Pathology,b Erasmus University. Reprint requests:Th. van Joost, MD, Department of Dermato-Venereology, Erasmus UniversityRotterdam, Dr. Molewaterplein40, 3015 GD Rotterdam, The Netherlands.
16/4/12753
Fig. 1. Vasculitis-like skin reactions on face as result of topical 5% benzoyl peroxide (Benzac W 5%). 359
360
v a n J o o s t et al.
Journal of the American Academy of Dermatology
Fig. 2. Photomicrograph of biopsy specimen at site of patch test reaction to 5% benzoyl peroxide. Capillaries are surrounded by lymphocytic infiltrate. (Hematoxylin-eosin stain; • 120.)
Fig. 3. Detail of vascular changes after patch test with 5% benzoyl peroxide. (Hematoxylin-eosin stain; •
woman (Fig. 1). She admitted having used 5% benzoyl peroxide gel (Benzac W 5%). After the patient stopped treatment, the lesions cleared in 5 weeks. Skin tests to Benzac W 5%, 1% and 5% benzoyl peroxide in petrolatum, and the European standard (International Contact Dermatitis Research Group) battery 1,2 were performed. Positive reactions to rosha (48 hours, +; 72 hours, ++); Benzac W 5% (48 hours, +; 72 hours, ++); and 5% benzoyl peroxide in petrolatum (48 hours, - ; 72 hours, +) were observed. No reaction to 1% benzoyl peroxide in petrolatum was noted. The positive reactions to Benzac W 5% and to 5% benzoyl peroxide in petrola-
turn clinically resembled the lesions on the face, but purpura was less evident. Both these reactions persisted for 96 hours and did not itch. A skin biopsy specimen was obtained from the site of the patch test reaction to Benzac W 5% (at 72 hours) for light and electron microscopy. Under light microscopy the epidermis revealed focal parakeratosis but the typical features of acute eczema were absent (Fig. 2). The capillaries showed endothelial swelling with obfiteration of their lumina and were surrounded by lymphocytes, macrophages, a few eosinophils, and prominent edema. No extravasation of erythrocytes was observed (Fig. 3). The
Volume 22 Number 2, Part 2 February 1990
Purpuric contact dermatitis to benzoyl peroxide
361
Fig. 4. Electron micrograph of biopsy specimen from site of patch test reaction to 5% benzoyl peroxide. Note swollen and enlarged endothelial ceils bulging into obliterated vascular lumen (asterisk). Nuclei (N) show nucleoplasm shrinkage. Cytoplasmic inclusions (CI) are found mainly around nuclei. Capillary basement membrane is unaltered (arrow), and pericytes (P) are normal. (•
vascular wall showed no fibrinoid necrosis. The deeper blood vessels were normal. Stainings were negative for iron or abnormal melanin deposition. On electron microscopy lymphocytes and rnacrophages were seen in connection with the capillary vessels.The endothelial cells showed a marked increase in cytoplasm with vacuoles of varying sizes, distended endoplasmic reticulum, and an increased number of free ribosomes (Fig. 4). The swollen rounded and enlarged endothelial cells bulged into the obliterated vascular lumen. In many endothelial cells dense cytoplasmic inclusions of varying sizes, mostly around the nucleus, were seen and were probably consistent with the lysosomal degeneration of the capillary endothelial cells. The nuclei showed shrinkage and condensation of the nucleoplasm. The capillary basement membrane (Fig. 4) and the pericytes were normal.
nuclear cell infiltrate with eosinophils but with obliterated capillary lumina (Figs. 3 and 4). A similar histologic appearance has been described in a patient with a petechial primary irritant dermatitis to cobalt. 5 We observed that at the ultrastructural level the capillary basement membranes remained unaltered, but a severe degeneration of the capillary endothelial ceils was apparent. This finding may indicate that a primary and selective toxic effect on the capillary endothetium led to a pericapillary infiltration. Alternatively, a primary antigen-induced lymphocytic reaction in the pericapillary region could liberate toxic lymphokines and may be directly responsible for the endothelial damage.
DISCUSSION
REFERENCES
We believe that the designation purpuric contact dermatitis is most appropriate. Purpuric contact dermatitis as a result of benzoyl peroxide has not been reported previously.3,4 In typical allergic contact dermatitis, in addition to spongiosis and epidermal exocytosis of lymphocytes, the vascular changes are characterized by a perivascular mononuclear infiltrate and capillary vasodilation. In contrast, in our patient the epidermis was normal, with a predominant pericapillary mono-
1. Malten KE, Nater JD, van Ketel WG. Patch-testing guidelines. Nijmegen, The Netherlands: Dekker en Van de Vegt, 1976. 2. van Joost Th, Stolz E, van der Hock JCS, et at. Shifts of delayed immune response to persulphates and other allergens. Contact Dermatitis 1984;11:159-62. 3. Lindemayr H, Orobi! M. Contact sensitization to benzoyl peroxide, Contact Dermatitis 1981;7:137-40. 4. Rietsehe RL, Duncan SH. Benzoyl peroxide reactions in an acne study group. Contact Dermatitis 1982;8:323-6. 5. Schmidt H, Larsen FS, Larsen PO, et al. Petechial reaction following patch testing with cobalt. Contact Dermatitis 1980;6:91-4,
8.
9. 10. 11. 12. 13. 14.
the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE. Rheum Int 1985;5:91-3. Harris EN, Asherson RA, Gharavi AE, et al. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibodies. Br J Haematol 1985; 59:227-30. Hughes GRV. Connective tissue disease and the skin. Clin Exp Dermatol 1984;9:535-44. Conley CL, Hartman RC. A haemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952;31:621-2. Boxer M, Ellman L, Carvalho A. The lupus anticoagulant. Arthritis Rheum 1976;19:1244-8. Schleider MA, Nachman RL, Jaffee EA, et al. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. Harris EN, HughesGRV.Antiphospholipidantibodies. In: McCarty D J, ed. Arthritis and allied conditions. 1 lth ed. Philadelphia: Lea & Febiger (In press). Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobin MX coagulation inhibitor with phospholipid specificity: mechanism of a lupus anticoagulant. J Clin Invest 1980;66:397-405.
Cutaneous necrosis with eardiolipin antibodies 15. Carreras LO, Defreyn J, Machin SJ, et al. Arterial thrombosis, intrauterine death and lupus anticoagulant: detection of immunoglobulin interfering with prostacyclin formation. Lancet 1981;1:244-6. 16. Cosgriff TM, Martin BA. Low functional and high antigenic antithrombin III level in a patient with the lupus anticoagulant and recurrent thrombosis. Arthritis Rheum 1981 ;24:94-6. 17. Sanfelippo M J, Drayna CJ. Prekallikrein inhibition associated with the lupus anticoagulant: a mechanism of thrombosis. Am J Clin Pathol 1982;77:275-9. 18. Harris EN, Hughes GRV, Gharavi AE. Anticardiolipin antibodies and the lupus anticoagulant. Clin Exp Rheumatol 1986;4:187-90. 19. Dodd H J, Sarkany l, O'Shaughnessy D. Widespread cutaneous necrosis associated with the lupus anticoagulant. Clin Exp Dermatol 1985;10:581-6. 20. Johansson EA, Niemi KM, Mustakallio KK. A peripheral vascular syndrome overlapping with systemic lupus erythematosus. Dermatologica 1977;155:257-67. 21. Lockshin MD.Anticardiolipinantibodies [Editorial].Arthritis Rheum 1987;30:471-2.
Purpuric contact dermatitis to benzoyl peroxide T h e o d o o r van Joost, M D , a Jos~ van Ulsen, M D , a Voijislav D. Vuzevsld, M D , b B e r n a r d N a a f s , M D , a and B h u p e n d r a T a n k , P h D a Rotterdam, The Netherlands Patch test reactions in a patient with purpuric contact dermatitis to 5% benzoyl peroxide are described. Alterations of the capillary endothelium included obliteration of the lumina with perivascular mononuclear cell infiltrates. There were no epidermal alterations. These observations are discussed with reference to the data in the literature on vascular damage in "dermal" contact dermatitis. (J AM ACAO DERMATOL 1990;22:359-61.) W e report our light and electron microscopy observations in a patient with a persistent purpuric c~ dermatitis caused by a d r u g containing benzoyl peroxide.
CASE R E P O R T An acute nonpruritic eruption characterized by infiltrated erythematous papules with focal purpura developed on the cheeks and the chin of a 22-year-old Asian From tile Departments of Dermato-Venereologya and Clinical Pathology,b Erasmus University. Reprint requests:Th. van Joost, MD, Department of Dermato-Venereology, Erasmus UniversityRotterdam, Dr. Molewaterplein40, 3015 GD Rotterdam, The Netherlands.
16/4/12753
Fig. 1. Vasculitis-like skin reactions on face as result of topical 5% benzoyl peroxide (Benzac W 5%). 359
360
v a n J o o s t et al.
Journal of the American Academy of Dermatology
Fig. 2. Photomicrograph of biopsy specimen at site of patch test reaction to 5% benzoyl peroxide. Capillaries are surrounded by lymphocytic infiltrate. (Hematoxylin-eosin stain; • 120.)
Fig. 3. Detail of vascular changes after patch test with 5% benzoyl peroxide. (Hematoxylin-eosin stain; •
woman (Fig. 1). She admitted having used 5% benzoyl peroxide gel (Benzac W 5%). After the patient stopped treatment, the lesions cleared in 5 weeks. Skin tests to Benzac W 5%, 1% and 5% benzoyl peroxide in petrolatum, and the European standard (International Contact Dermatitis Research Group) battery 1,2 were performed. Positive reactions to rosha (48 hours, +; 72 hours, ++); Benzac W 5% (48 hours, +; 72 hours, ++); and 5% benzoyl peroxide in petrolatum (48 hours, - ; 72 hours, +) were observed. No reaction to 1% benzoyl peroxide in petrolatum was noted. The positive reactions to Benzac W 5% and to 5% benzoyl peroxide in petrola-
turn clinically resembled the lesions on the face, but purpura was less evident. Both these reactions persisted for 96 hours and did not itch. A skin biopsy specimen was obtained from the site of the patch test reaction to Benzac W 5% (at 72 hours) for light and electron microscopy. Under light microscopy the epidermis revealed focal parakeratosis but the typical features of acute eczema were absent (Fig. 2). The capillaries showed endothelial swelling with obfiteration of their lumina and were surrounded by lymphocytes, macrophages, a few eosinophils, and prominent edema. No extravasation of erythrocytes was observed (Fig. 3). The
Volume 22 Number 2, Part 2 February 1990
Purpuric contact dermatitis to benzoyl peroxide
361
Fig. 4. Electron micrograph of biopsy specimen from site of patch test reaction to 5% benzoyl peroxide. Note swollen and enlarged endothelial ceils bulging into obliterated vascular lumen (asterisk). Nuclei (N) show nucleoplasm shrinkage. Cytoplasmic inclusions (CI) are found mainly around nuclei. Capillary basement membrane is unaltered (arrow), and pericytes (P) are normal. (•
vascular wall showed no fibrinoid necrosis. The deeper blood vessels were normal. Stainings were negative for iron or abnormal melanin deposition. On electron microscopy lymphocytes and rnacrophages were seen in connection with the capillary vessels.The endothelial cells showed a marked increase in cytoplasm with vacuoles of varying sizes, distended endoplasmic reticulum, and an increased number of free ribosomes (Fig. 4). The swollen rounded and enlarged endothelial cells bulged into the obliterated vascular lumen. In many endothelial cells dense cytoplasmic inclusions of varying sizes, mostly around the nucleus, were seen and were probably consistent with the lysosomal degeneration of the capillary endothelial cells. The nuclei showed shrinkage and condensation of the nucleoplasm. The capillary basement membrane (Fig. 4) and the pericytes were normal.
nuclear cell infiltrate with eosinophils but with obliterated capillary lumina (Figs. 3 and 4). A similar histologic appearance has been described in a patient with a petechial primary irritant dermatitis to cobalt. 5 We observed that at the ultrastructural level the capillary basement membranes remained unaltered, but a severe degeneration of the capillary endothelial ceils was apparent. This finding may indicate that a primary and selective toxic effect on the capillary endothetium led to a pericapillary infiltration. Alternatively, a primary antigen-induced lymphocytic reaction in the pericapillary region could liberate toxic lymphokines and may be directly responsible for the endothelial damage.
DISCUSSION
REFERENCES
We believe that the designation purpuric contact dermatitis is most appropriate. Purpuric contact dermatitis as a result of benzoyl peroxide has not been reported previously.3,4 In typical allergic contact dermatitis, in addition to spongiosis and epidermal exocytosis of lymphocytes, the vascular changes are characterized by a perivascular mononuclear infiltrate and capillary vasodilation. In contrast, in our patient the epidermis was normal, with a predominant pericapillary mono-
1. Malten KE, Nater JD, van Ketel WG. Patch-testing guidelines. Nijmegen, The Netherlands: Dekker en Van de Vegt, 1976. 2. van Joost Th, Stolz E, van der Hock JCS, et at. Shifts of delayed immune response to persulphates and other allergens. Contact Dermatitis 1984;11:159-62. 3. Lindemayr H, Orobi! M. Contact sensitization to benzoyl peroxide, Contact Dermatitis 1981;7:137-40. 4. Rietsehe RL, Duncan SH. Benzoyl peroxide reactions in an acne study group. Contact Dermatitis 1982;8:323-6. 5. Schmidt H, Larsen FS, Larsen PO, et al. Petechial reaction following patch testing with cobalt. Contact Dermatitis 1980;6:91-4,
