- Email: [email protected]
Stevens-Johnson syndrome: a case report
ARTICLE IN PRESS Research letters There is a consensus in the literature that wheezing in the cervical region is characteristic of patients with VCD and is extremely important for the disease’s diagnosis, as occurred in the present case. As reported, although our patient was unable to perform pulmonary function tests, the diagnosis of VCD was confirmed through laryngoscopy. The treatment of VCD consists of psychotherapy and speech therapy. Respiratory exercises typically used for treating hyperfunctional voice disorders are employed in order to reduce laryngeal muscle tension. Since beta-2 agonists and inhaled corticosteroids tend to produce poor results, they should be used only in patients with concomitant asthma. A multidisciplinary team is needed in order to increase the chances of treatment success.1,2,4 Some authors have suggested that this condition is a type of conversion disturbance, which is not fictitious because the patient can neither consciously control the dysfunction nor voluntarily reproduce the paradoxal movements.1,2,4 Despite the association with psychiatric disorders, there have been no previous reports of VCD in patients with schizophrenia. This disease is essentially characterized by fragmentation of thought processes and, perhaps, neuropsychological mechanisms could trigger DPV. There is no known cure for it, but treatment can provide some degree of symptom relief, allowing patients to live a satisfactory, productive life.9,10 We highlight the fact that VCD is under-diagnosed, and that many patients are overmedicated for asthma. Therefore, the hypothesis of this diagnosis should always be considered.
References 1. Newman KB, Mason UG, Shmaling KB. Clinical features of vocal cord dysfunction. Am J Respir Crit Care Med. 1995;152:1382–6.
219 2. Corren J, Newman KB. Vocal cord dysfunction mimicking bronchial asthma. Postgrad Med. 1992;92:153–6. 3. Giavina-Bianchi P, Pinto LHE, Sayed S, Cukier A, Kalil J. Development of a specific questionnaire for the suspicion of DPV. In: AAAAI Annual Meeting. San Diego. J Allergy Clin Immunol 2007;119:S165. 4. O’Connell MA, Sklarew PR, Goodman DL. Spectrum of presentation of paradoxic vocal cord montion in ambulatory patients. Ann Allergy. 1995;74:341–4. 5. Koufman JA. The differential diagnosis of paradoxical vocal cord movement. Visible Voice. 1994;3:49–53. 6. Trudeau MD. Paradoxical vocal cord dysfunctional among juveniles. Voice and Voice Disorders, SID 3. Newsletter. 1998;8: 11–8. 7. Hicks DM, Ours TM, Abelson TI, Vaezi MF, Richter JE. The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice. 2002;16:564–79. 8. Morrison M, Rammage L, Emami AJ. The irritable larynx syndrome. J Voice. 1999;13:447–55. 9. Mohamed S, Rosenheck R, Swatz M, Stroups S, Lieberman JA, Keefe RS. Relationship of cognition and psychopathology to functional impairment in schizophrenia. Am J Psychiatry. 2008; 165:978–87. 10. Freedman R. Schizophrenia. New Engl J Med. 2003;349: 1738–49.
C. Bisaccioni, E. Cajuela, R. Ca ˆmara Agondi, J. Kalil, P. Giavina-Bianchi Clinical Immunology and Allergy Division, Sa ˜o Paulo University, Sa˜o Paulo, Brasil Corresponding author:
E-mail address: [email protected] (P. Giavina-Bianchi)
doi:10.1016/j.aller.2009.02.002
Stevens-Johnson syndrome: a case report To the Editor: Stevens-Johnson syndrome (SJS) is a life-threatening vesiculobullous disease characterized by an acute eruption that involves the skin and mucous membranes. Various etiologic factors have been implicated as a cause of SJS, including infection, vaccination, drugs, systemic diseases, physical agents, and food. Drugs are the most commonly blamed. The incidence of SJS is estimated to be between 1.1 and 7.1 cases per million person-years.1 SJS is currently considered to be a part of bullous disease syndromes [SJS, SJStoxic epidermal necrolysis (TEN) overlap syndrome, and TEN] in which keratinocyte cell death results in subepidermal separation. In SJS, skin detachment is limited to less than 10% of the body surface area (BSA). TEN requires skin detachment of more than 30% of the BSA. An overlap group of SJS/TEN has been defined with erosions between 10% and 3 0% of the BSA.1–3 The pathogenesis of SJS has yet to be clarified.
We report a 10-year-old male patient who was admitted to our department with a widespread bullous, erythematous pruritic eruption, bilateral conjunctivitis, oedema of lips and eyelids, haemorrhagic crusts of the lips, superficial erosions of the hard palate, an ulceration on the penile meatus (Fig. 1), and high fever (38.2 1C). The symptoms first started 2 days before, approximately 7 h after intramuscular administration of the 2nd dose of cefazolin (2 500 mg, i.m) which had been prescribed with the diagnosis of acute pharyngitis. He did not take any other drug apart from the antibiotics. He had no history of adverse drug reactions and had not been treated with cefazolin before. Other personal and family history was unremarkable. The clinical diagnosis of drug induced SJS was made with epidermal detachment of 7–8% of total body surface area.1–3 Laboratory results on admission revealed WBC count, 2330/mm3; lymphocytes, 25%; platelets, 160000/mm3; erythrocyte sedimentation rate (ESR), 36/h; C-reactive protein, 5.08 mg/dl (0-1); aspartate aminotransferase (AST), 54 U/l (15-41); alanine aminotransferase (ALT), 16U/ l (14-54). Blood urea nitrogen (BUN), 41 mg/dl; creatinin and
ARTICLE IN PRESS 220
Research letters
Figure 2 Squamous epithelium on skin surface is hyperkeratotic. Note full-thickness epithelial necrosis and dermoepidermal separation on the left corner as well as sparse lymphocyte exocytosis into the epithelium and sparse perivascular leukocyte infiltration of the upper dermis. H&E, X50.
Figure 1 Vesiculo-bullous skin and mucous membrane lesions with detachment of epidermis.
urine analysis were normal. Serum Na, 131 mEq/l; K, 4.6 mEq/l; total protein, 5.7 gr/dl; albumin, 2.6 gr/dl. Haemoculture and swab culture from skin lesions were negative. Serum cold haemagglutinin titers and viral serology were negative. With immunophenotypic analysis (Coulter Epics XL), absolute numbers of peripheral blood lymphocytes were calculated as: CD19+, 136; CD4+, 156; CD8+, 236 (CD4+/CD8+ ratio, 0.66), and CD3CD16+ CD56+ (NK cells), 29 cells/ml. The predominant phenotype of the gated lymphocytes among blister fluid mononuclear cells was CD8+ (48.7%). Other cell subsets were CD19+ (0.2%), CD4+ (25.2%), and NK cells (3.4%). Microscopically, the surface epithelium of the skin biopsy was hyperkeratotic. There was full-thickness epithelial necrosis, dermo-epidermal separation, as well as sparse lymphocyte exocytosis into the epithelium, and sparse perivascular leukocyte infiltration of the upper dermis (Fig. 2). The epidermal lymphocytes showed labelling with anti-CD8 by immunohistochemical staining. These changes were considered to be consistent with SJS (Fig. 3). The patient’s symptoms began to improve after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy. Corticosteroid dose was gradually tapered after the 4th day of treatment. He
Figure 3 Note spare anti-CD8 immunoreactive lymphocytes in the epithelium. CD8, x100.
had gastrointestinal bleeding during his hospitalisation. This is attributed to the gastrointestinal system involvement in SJS. The patient was discharged with markedly clinical improvement 12 days after admission. Follow-up visits were conducted by our Ophthalmology Clinic for his dry eye syndrome as a long term effect of SJS. The patient was patch tested with cefazolin 2 months after the reaction. However, he removed the test tape after 24 h because of itching and did not return for evaluation. SJS is an uncommon and potentially serious mucocutaneous disease. More than 100 drugs have been associated with the development of SJS and TEN.4 Cefazolin would be responsible for inducing SJS in our patient. The role of corticosteroid therapy in SJS is still controversial.1,2,5 Our patient’s symptoms improved after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy.
ARTICLE IN PRESS Research letters The pathogenesis of SJS has yet to be clarified. The scenario suggested by today’s literature points towards drug-specific CD8+cytotoxic T cells utilising perforin/granzyme B trigger keratinocyte apoptosis.6 In TEN, several studies stated a predominance of CD8+ T lymphocytes along dermoepidermal junction, in the epidermis, or in the blister fluid of early blisters.7–11 In keeping with these findings, Behrendt et al.12 reported a higher percentage of perforin positive CD8+ T lymphocytes in PBMC of patients with SJS on the day of their admission than in healthy donors. Similarly, Psodas et al.13 showed increased mRNA expression of perforin and granzyme B in PBMC of SJS and TEN patients compared to controls and suggested that there may even be association between disease severity and perforin and granzyme B levels. The expression levels were markedly higher in mononuclear cells obtained from blister fluid compared to PBMC, suggesting local production of both of these transcripts.6 These findings lend further support to the theory that keratinocyte apoptosis is triggered by drugspecific cytotoxic T lymphocytes (CTL) using the perforin/ granzyme B pathway. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. However, the cellular source of sFasL remains controversial, with both peripheral lymphocytes and keratinocytes themselves as potential candidates.2,6 Our data are in agreement with previous reports of the presence of CD8+ T cells at the site of skin lesions in patients with SJS,7–12 and further support the involvement of cytotoxic CD8+T cells in eliciting tissue damage in SJS. We concluded that the cells contained in the blister fluid during SJS would provide an interesting way to investigate the immune mechanisms in bullous drug reactions.
References
221
6.
7.
8.
9.
10.
11.
12.
13.
Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis. Ann Allergy. 1994;73:27–34. Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME. Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev. 2008;7:598–605. Miyauchi H, Hosokawa H, Akaeda T, Iba H, Asada Y. T-cell subsets in drug-induced toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol. 1991;127:851–5. Villada G, Roujeau JC, Cle´rici T, Bourgault I, Revuz J. Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases. Arch Dermatol. 1992;128:50–3. Correia O, Delgado L, Ramos JP, Resende C, Torrinha JA. Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. Arch Dermatol. 1993;129:466–8. Le Cleach L, Delaire S, Boumsell L, Bagot M, Bourgault-Villada I, Bensussan A, et al. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors. Clin Exp Immunol. 2000;119:225–30. Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, et al. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004;114:1209–15. Behrendt C, Gollnick H, Bonnekoh B. Up-regulated perforin expression of CD8+ blood lymphocytes in generalized non-anaphylactic drug eruptions and exacerbated psoriasis. Eur J Dermatol. 2000;10:365–9. Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109:155–61.
M. Yazicioglua,, B. Iscanb, B. Turgutc, O. Yalcind a
1. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94:419–36. 2. Khalili B, Bahna SL. Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis. Ann Allergy Asthma Immunol. 2006;97:272–80. 3. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int. 2006;55: 9–16. 4. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–7. 5. Patterson R, Miller M, Kaplan M, Doan T, Brown J, Detjen P, et al. Effectiveness of early therapy with corticosteroids in doi:10.1016/j.aller.2009.02.003
Department of Pediatric Allergy, Trakya University, Faculty of Medicine, Edirne, Turkey b Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey c Department of Internal Medicine, Trakya University, Faculty of Medicine, Edirne, Turkey d Department of Pathology, Trakya University, Faculty of Medicine, Edirne, Turkey Corresponding author.
E-mail address: [email protected] (M. Yazicioglu)
References 1. Newman KB, Mason UG, Shmaling KB. Clinical features of vocal cord dysfunction. Am J Respir Crit Care Med. 1995;152:1382–6.
219 2. Corren J, Newman KB. Vocal cord dysfunction mimicking bronchial asthma. Postgrad Med. 1992;92:153–6. 3. Giavina-Bianchi P, Pinto LHE, Sayed S, Cukier A, Kalil J. Development of a specific questionnaire for the suspicion of DPV. In: AAAAI Annual Meeting. San Diego. J Allergy Clin Immunol 2007;119:S165. 4. O’Connell MA, Sklarew PR, Goodman DL. Spectrum of presentation of paradoxic vocal cord montion in ambulatory patients. Ann Allergy. 1995;74:341–4. 5. Koufman JA. The differential diagnosis of paradoxical vocal cord movement. Visible Voice. 1994;3:49–53. 6. Trudeau MD. Paradoxical vocal cord dysfunctional among juveniles. Voice and Voice Disorders, SID 3. Newsletter. 1998;8: 11–8. 7. Hicks DM, Ours TM, Abelson TI, Vaezi MF, Richter JE. The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice. 2002;16:564–79. 8. Morrison M, Rammage L, Emami AJ. The irritable larynx syndrome. J Voice. 1999;13:447–55. 9. Mohamed S, Rosenheck R, Swatz M, Stroups S, Lieberman JA, Keefe RS. Relationship of cognition and psychopathology to functional impairment in schizophrenia. Am J Psychiatry. 2008; 165:978–87. 10. Freedman R. Schizophrenia. New Engl J Med. 2003;349: 1738–49.
C. Bisaccioni, E. Cajuela, R. Ca ˆmara Agondi, J. Kalil, P. Giavina-Bianchi Clinical Immunology and Allergy Division, Sa ˜o Paulo University, Sa˜o Paulo, Brasil Corresponding author:
E-mail address: [email protected] (P. Giavina-Bianchi)
doi:10.1016/j.aller.2009.02.002
Stevens-Johnson syndrome: a case report To the Editor: Stevens-Johnson syndrome (SJS) is a life-threatening vesiculobullous disease characterized by an acute eruption that involves the skin and mucous membranes. Various etiologic factors have been implicated as a cause of SJS, including infection, vaccination, drugs, systemic diseases, physical agents, and food. Drugs are the most commonly blamed. The incidence of SJS is estimated to be between 1.1 and 7.1 cases per million person-years.1 SJS is currently considered to be a part of bullous disease syndromes [SJS, SJStoxic epidermal necrolysis (TEN) overlap syndrome, and TEN] in which keratinocyte cell death results in subepidermal separation. In SJS, skin detachment is limited to less than 10% of the body surface area (BSA). TEN requires skin detachment of more than 30% of the BSA. An overlap group of SJS/TEN has been defined with erosions between 10% and 3 0% of the BSA.1–3 The pathogenesis of SJS has yet to be clarified.
We report a 10-year-old male patient who was admitted to our department with a widespread bullous, erythematous pruritic eruption, bilateral conjunctivitis, oedema of lips and eyelids, haemorrhagic crusts of the lips, superficial erosions of the hard palate, an ulceration on the penile meatus (Fig. 1), and high fever (38.2 1C). The symptoms first started 2 days before, approximately 7 h after intramuscular administration of the 2nd dose of cefazolin (2 500 mg, i.m) which had been prescribed with the diagnosis of acute pharyngitis. He did not take any other drug apart from the antibiotics. He had no history of adverse drug reactions and had not been treated with cefazolin before. Other personal and family history was unremarkable. The clinical diagnosis of drug induced SJS was made with epidermal detachment of 7–8% of total body surface area.1–3 Laboratory results on admission revealed WBC count, 2330/mm3; lymphocytes, 25%; platelets, 160000/mm3; erythrocyte sedimentation rate (ESR), 36/h; C-reactive protein, 5.08 mg/dl (0-1); aspartate aminotransferase (AST), 54 U/l (15-41); alanine aminotransferase (ALT), 16U/ l (14-54). Blood urea nitrogen (BUN), 41 mg/dl; creatinin and
ARTICLE IN PRESS 220
Research letters
Figure 2 Squamous epithelium on skin surface is hyperkeratotic. Note full-thickness epithelial necrosis and dermoepidermal separation on the left corner as well as sparse lymphocyte exocytosis into the epithelium and sparse perivascular leukocyte infiltration of the upper dermis. H&E, X50.
Figure 1 Vesiculo-bullous skin and mucous membrane lesions with detachment of epidermis.
urine analysis were normal. Serum Na, 131 mEq/l; K, 4.6 mEq/l; total protein, 5.7 gr/dl; albumin, 2.6 gr/dl. Haemoculture and swab culture from skin lesions were negative. Serum cold haemagglutinin titers and viral serology were negative. With immunophenotypic analysis (Coulter Epics XL), absolute numbers of peripheral blood lymphocytes were calculated as: CD19+, 136; CD4+, 156; CD8+, 236 (CD4+/CD8+ ratio, 0.66), and CD3CD16+ CD56+ (NK cells), 29 cells/ml. The predominant phenotype of the gated lymphocytes among blister fluid mononuclear cells was CD8+ (48.7%). Other cell subsets were CD19+ (0.2%), CD4+ (25.2%), and NK cells (3.4%). Microscopically, the surface epithelium of the skin biopsy was hyperkeratotic. There was full-thickness epithelial necrosis, dermo-epidermal separation, as well as sparse lymphocyte exocytosis into the epithelium, and sparse perivascular leukocyte infiltration of the upper dermis (Fig. 2). The epidermal lymphocytes showed labelling with anti-CD8 by immunohistochemical staining. These changes were considered to be consistent with SJS (Fig. 3). The patient’s symptoms began to improve after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy. Corticosteroid dose was gradually tapered after the 4th day of treatment. He
Figure 3 Note spare anti-CD8 immunoreactive lymphocytes in the epithelium. CD8, x100.
had gastrointestinal bleeding during his hospitalisation. This is attributed to the gastrointestinal system involvement in SJS. The patient was discharged with markedly clinical improvement 12 days after admission. Follow-up visits were conducted by our Ophthalmology Clinic for his dry eye syndrome as a long term effect of SJS. The patient was patch tested with cefazolin 2 months after the reaction. However, he removed the test tape after 24 h because of itching and did not return for evaluation. SJS is an uncommon and potentially serious mucocutaneous disease. More than 100 drugs have been associated with the development of SJS and TEN.4 Cefazolin would be responsible for inducing SJS in our patient. The role of corticosteroid therapy in SJS is still controversial.1,2,5 Our patient’s symptoms improved after initiation of intravenous methylprednisolone and hydroxizine in conjunction with supportive therapy.
ARTICLE IN PRESS Research letters The pathogenesis of SJS has yet to be clarified. The scenario suggested by today’s literature points towards drug-specific CD8+cytotoxic T cells utilising perforin/granzyme B trigger keratinocyte apoptosis.6 In TEN, several studies stated a predominance of CD8+ T lymphocytes along dermoepidermal junction, in the epidermis, or in the blister fluid of early blisters.7–11 In keeping with these findings, Behrendt et al.12 reported a higher percentage of perforin positive CD8+ T lymphocytes in PBMC of patients with SJS on the day of their admission than in healthy donors. Similarly, Psodas et al.13 showed increased mRNA expression of perforin and granzyme B in PBMC of SJS and TEN patients compared to controls and suggested that there may even be association between disease severity and perforin and granzyme B levels. The expression levels were markedly higher in mononuclear cells obtained from blister fluid compared to PBMC, suggesting local production of both of these transcripts.6 These findings lend further support to the theory that keratinocyte apoptosis is triggered by drugspecific cytotoxic T lymphocytes (CTL) using the perforin/ granzyme B pathway. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. However, the cellular source of sFasL remains controversial, with both peripheral lymphocytes and keratinocytes themselves as potential candidates.2,6 Our data are in agreement with previous reports of the presence of CD8+ T cells at the site of skin lesions in patients with SJS,7–12 and further support the involvement of cytotoxic CD8+T cells in eliciting tissue damage in SJS. We concluded that the cells contained in the blister fluid during SJS would provide an interesting way to investigate the immune mechanisms in bullous drug reactions.
References
221
6.
7.
8.
9.
10.
11.
12.
13.
Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis. Ann Allergy. 1994;73:27–34. Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME. Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev. 2008;7:598–605. Miyauchi H, Hosokawa H, Akaeda T, Iba H, Asada Y. T-cell subsets in drug-induced toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol. 1991;127:851–5. Villada G, Roujeau JC, Cle´rici T, Bourgault I, Revuz J. Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases. Arch Dermatol. 1992;128:50–3. Correia O, Delgado L, Ramos JP, Resende C, Torrinha JA. Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. Arch Dermatol. 1993;129:466–8. Le Cleach L, Delaire S, Boumsell L, Bagot M, Bourgault-Villada I, Bensussan A, et al. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors. Clin Exp Immunol. 2000;119:225–30. Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, et al. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004;114:1209–15. Behrendt C, Gollnick H, Bonnekoh B. Up-regulated perforin expression of CD8+ blood lymphocytes in generalized non-anaphylactic drug eruptions and exacerbated psoriasis. Eur J Dermatol. 2000;10:365–9. Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109:155–61.
M. Yazicioglua,, B. Iscanb, B. Turgutc, O. Yalcind a
1. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94:419–36. 2. Khalili B, Bahna SL. Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis. Ann Allergy Asthma Immunol. 2006;97:272–80. 3. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int. 2006;55: 9–16. 4. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–7. 5. Patterson R, Miller M, Kaplan M, Doan T, Brown J, Detjen P, et al. Effectiveness of early therapy with corticosteroids in doi:10.1016/j.aller.2009.02.003
Department of Pediatric Allergy, Trakya University, Faculty of Medicine, Edirne, Turkey b Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey c Department of Internal Medicine, Trakya University, Faculty of Medicine, Edirne, Turkey d Department of Pathology, Trakya University, Faculty of Medicine, Edirne, Turkey Corresponding author.
E-mail address: [email protected] (M. Yazicioglu)