[en] The treatment of drug-induced toxic epidermal necrolysis (TEN) remains unsatisfactory. Intravenous immunoglobulins (IVIg) and intravenous cyclosporin A (CsA) have shown some efficacy in short series of patients. We assessed the effects of IVIg and CsA on TEN lesional and apparently uninvolved skin using standard histology and immunohistochemistry. Cutaneous biopsies were taken from necrotic and clinically uninvolved TEN skin at admission (D1) before any treatment, and after a 5-day treatment (D5). Two IVIg-treated patients (0.75 g/kg/day), two CsA-treated patients (5 mg/kg/day) and two control patients only receiving supportive care were compared. Biopsies were examined by standard histology and immunohistochemistry using antibodies directed to CD68 antigen (macrophages), CD45R0 antigen (activated T lymphocytes), Factor XIIIa (dermal dendrocytes) and the CD95 receptor (apoptosis marker). The different cell densities were evaluated by computerized image analysis. The clinical outcomes with the different treatments were also recorded. There was no obvious difference in the duration of hospitalization in intensive care unit between the three groups but one patient passed away in each of the IVIg- and CsA-groups. At D5, no differences were found between the three groups in the histological and clinical rate of re-epithelialization, and in the evolution of T lymphocyte, macrophage and dendrocyte densities in the epidermis and dermis. However, the expression of the CD95 receptor was similarly and strongly abated at D5 in the epidermis of IVIg- and CsA-treated patients, while it was conversely increased in the two patients under supportive care only. Such a difference was found both in necrotic and uninvolved sites. IVIg and CsA treatments thus appeared to exert no obvious effect on the inflammatory infiltrate, but both abated the expression of the CD95 receptor in the skin of TEN patients. This effect did not seem sufficient to fully reverse the clinical evolution of the disease. It is inferred that IVIg and CsA do not completely abate the TEN process.
Disciplines :
Dermatology
Author, co-author :
Paquet, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Jacob, Eric; Centre Hospitalier Universitaire de Liège - CHU > Soins Intensifs
Damas, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
Pirson, J.; Intensive care medicine, burn center, Brussels Military Hospital,
Pierard, Gérald ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Language :
English
Title :
Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug-induced toxic epidermal necrolysis.
Arevalo J, Lorente JA, Gonzalez-Herrada C, Jimenez-Reyes J (2000) Treatment of toxic epidermal necrolysis with cyclosporin A. J Trauma Inj Inf Crit Care 48:473-478
Bachot N, Revuz J, Roujeau JC (2003) Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis. Arch Dermatol 139:33-36
Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P (2000) SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 45:149-153
Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC (1993) Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme. Arch Dermatol 129:92-96
Frangogiannis NG, Boridy F, Mazhar M, Mathews R, Gangopadhyay S, Cate T (1996) Cyclophosphamide in the treatment of toxic epidermal necrolysis. South Med J 89:1001-1003
Fulda S, Sieverts H, Friesen C, Herr I, Debatin KM (1997) The CD95 (APO-1Fas) system mediates drug-induces apoptosis in neuroblastoma cells. Cancer Res 57:3823-3829
Herndon D (1995) Toxic epidermal necrolysis: a systemic and dermatologic disorder best treated with standard treatment protocols in burns intensive care units without the prolonged use of corticosteroids. J Am Coll Surg 180:340-342
Jarrett P, Rademaker M, Havill J, Pullon H (1997) Toxic epidermal necrolysis treated with cyclosporin and granulocyte colony simulating factor. Clin Exp Dermatol 22:146-147
Magina S, Lisboa C, Goncalves E, Conceicao P, Leal U, Mesquita-Guimaraes J (2000) A case of toxic epidermal necrolysis treated with intravenous immunoglobulin. Br J Dermatol 142:177-178
Mockenhaupt M, Norgauer J (2002) Cutaneous adverse drug reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis. Allergy Clin Immunol Int 14:143-150
Murdoch SR, Fenton DA (1997) Toxic epidermal necrolysis and cyclosporin. Clin Exp Dermatol 22:250-256
Paquet P, Arrese Estrada J, Piérard GE (1992) Oral cyclosporin and alopecia aerata. Dermatology 105:314-315
Paquet P, Jacob E, Damas P, Piérard GE (2001) Treatment of drug-induced toxic epidermal necrolysis (Lyell's syndrome) with intravenous human immunoglobulins. Burns 27:652-655
Paquet P, Piérard GE (1999) Would cyclosporin A be beneficial to mitigate drug-induced toxic epidermal necrolysis? Dermatology 198:198-202
Paquet P, Piérard GE (2002) Differential patomechanisms of epidermal necrolytic blistering diseases. Int J Mol Med 10:695-699
Paquet P, Piérard GE (2002) Keratinocyte injury in drug-induced toxic epidermal necrolysis: simultaneous but distinct topographic expression of CD95R and calprotectin. Int J Mol Med 10:145-147
Paquet P, Piérard GE, Quatresooz P (2005) Novel treatments for drug-induced toxic epidermal necrolysis (Lyell's syndrome). Int Arch Allergy Immunol 136:205-216
Phan TG, Wang R, Crotty T, Adelstein S (1999) Toxic epidermal necrolysis treated with intravenous gammaglobulin. Australas J Dermatol 40:153-157
Prins C, Kerdel FA, Padilla RS, Hunziker T, Chimenti S, Viard I et al (2003) Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins. Arch Dermatol 139:26-32
Renfro L, Grant-Kels J, Daman LA (1989) Drug-induced toxic epidermal necrolysis treated with cyclosporin. Int J Dermatol 28:441-444
Roujeau JC, Guillaume JC, Fabre JP, Penso D, Flechet ML, Girre JP (1990) Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-1985. Arch Dermatol 126:37-42
Sanclemente G, De la Roche C, Escobar C, Fabella R (1998) Pentoxifylline in toxic epidermal necrolysis and Stevens-Johnson syndrome. Int J Dermatol 38:873-874
Stella M, Cassano P, Bollero D, Clemente A, Giorio G (2001) Toxic epidermal necrolysis treated with intravenous high-dose immunoglobulins: our experience. Dermatology 203:45-49
Sullivan JR, Watson A (1996) Lamotrigine-induced toxic epidermal necrolysis treated with intravenous cyclosporin: a discussion of pathogenesis and immunosuppressive management. Australas J Dermatol 37:208-212
Szepietowki J, Wasik F, Szybejko-Machay G, May J (1997) Toxic epidermal necrolysis successfully treated with cyclosporin. Report of three cases. J Eur Acad Dermatol Venereol 9:169-172
Trautmann A, Akdis M, Schmid-Grendelmeier P, Disch R, Bröcker EB, Blaser K et al (2001) Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. J Allergy Clin Immunol 108:839-846
Trent JT, Kirsner RS, Romanelli P, Kerdel FA (2003) Analysis of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis using SCORTEN. Arch Dermatol 139:39-43
Tristani-Firouzi P, Petersen M, Saffle JR, Morris SE, Zone JJ (2002) Treatment of toxic epidermal necrolysis with intravenous immunoglobulin in children. J Am Acad Dermatol 47:548-552
Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D et al (1998) Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 282:490-493
Wolkenstein P, Latarjet P, Roujeau JC (1998) Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet 352:1586-1589
Zaki I, Patel S, Reed R, Dalziel KL (1995) Toxic epidermal necrolysis associated with severe hypocalcaemia, and treated with cyclosporin. Br J Dermatol 133:337-338