Supplemental Table: EMPACT syndrome in the literaturefor patients receiving cranial irradiation

Authors / Date of Publication / Number of cases (n) / Ages (years) / Tumor type / AED / Type of RT / Rash Type
Maiche et al.1 / 1985 / 4 / NR / Primary (n=3)
Metastatic (n=1) / Phenytoin / WBRT (n=4) / SJS (n=4)
Delattre et al.2 / 1988 / 8 / 30, 43, 35, 67, 55, 36, 59, 26 / Primary (n=2)
Metastatic (n=6) / Phenytoin / WBRT (n=8) / SJS (n=3)
EM (n=5)
Giroud et al.3 / 1990 / 1 / NR / Primary / Phenytoin / WBRT / EM
Rowe et al.4 / 1991 / 1 / 41 / Metastatic / Phenytoin / WBRT / TEN
Janinis et al.5 / 1993 / 4 / 44, 45, 48, 53 / Primary (n=1)
Metastatic (n=3) / Phenytoin / 3D CRT (n=1)
WBRT (n=3) / SJS (n=1)
TEN (n=3)
Borg et al.6 / 1995 / 1 / 55 / Metastatic / Phenytoin / WBRT / SJS
Cockey et al.7 / 1996 / 1 / 61 / Metastatic / Phenytoin / WBRT / SJS
Duncan et al.8 / 1999 / 1 / 53 / Metastatic / Phenobarbital / WBRT / SJS
Khafaga et al.9 / 1999 / 4 / 22, 41, 45, 56 / Primary (n=4) / Phenytoin / NR / SJS (n=2)
SJS/TEN (n=2)
Micali et al.10 / 1999 / 1 / 47 / Metastatic / Phenytoin / WBRT / SJS
Eralp et al.11 / 2001 / 1 / 28 / Metastatic / Phenytoin / WBRT / SJS
Trent et al.12 / 2001 / 2 / 62, 55 / Primary (n=1)
Metastatic (n=1) / Phenytoin
Carbamazepine / NR (n=2) / TEN (n=2)
Maldonado et al.13 / 2002 / 1 / 72 / Metastatic / Carbamazepine / WBRT / TEN
Aguiar et al.14 / 2004 / 1 / 52 / Metastatic / Phenytoin / WBRT / TEN
Ahmed et al.15 / 2004 / 3 / 23, 36, 46 / Metastatic (n=3) / Phenytoin / WBRT (n=3) / SJS
Dincbas et al.16 / 2004 / 1 / 65 / Metastatic / Phenytoin / WBRT / TEN
Whorl et al.17 / 2005 / 1 / 46 / Metastatic / Phenytoin / WBRT / EM
Aydin et al.18 / 2006 / 2 / 62 / Metastatic (n=2) / Phenytoin / WBRT (n=2) / SJS (n=2)
Fernandez et al.19 / 2007 / 1 / 76 / Metastatic / Phenytoin / WBRT / TEN
Barbosa et al.20 / 2008 / 1 / 60 / Metastatic / Phenytoin / WBRT / TEN
Ranu et al.21 / 2008 / 1 / 43 / Metastatic / Phenytoin / WBRT / TEN
Sarma22 / 2009 / 1 / 46 / Primary / Phenytoin / NR / SJS/TEN
Aydogan et al.23 / 2010 / 1 / 54 / Metastatic / Phenytoin / WBRT / EM
Kandil et al.24 / 2010 / 1 / 46 / Metastatic / Phenytoin / WBRT / SJS
Bilgili et al.25 / 2011 / 1 / 36 / Metastatic / Phenytoin / WBRT / EM
Fabbrocini et al.26 / 2013 / 2 / 42, 43 / Metastatic (n=2) / Phenobarbital / WBRT / SJS (n=2)

Abbreviations: RT, radiation therapy; AED, anti-epileptic drug;WBRT,whole-brain radiation therapy; 3D CRT, 3-dimensional conformal radiation therapy; SJS, Stevens-Johnson Syndrome; EM, erythema multiforme; TEN, toxic epidermal necrosis; NR, not reported.

Supplemental References

1.Maiche A, Teerenhovi L. Stevens-Johnson syndrome in patients receiving radiation therapy. Lancet. 1985;2:45.

2.Delattre JY, Safai B, Posner JB. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology. 1988;38:194-198.

3.Giroud M, Oriol P, Sgro M, et al. [Erythema multiforme induced by the combination of phenytoin and cerebral irradiation]. Therapie. 1990;45:23-25.

4.Rowe JE, Pina J, Sau P, Samlaska C, James W. Toxic epidermal necrolysis associated with diphenylhydantoin and cranial irradiation. Int J Dermatol. 1991;30:747-749.

5.Janinis J, Panagos G, Panousaki A, et al. Stevens-Johnson syndrome and epidermal necrolysis after administration of sodium phenytoin with cranial irradiation. Eur J Cancer. 1993;29A:478-479.

6.Borg MF, Probert JC, Zwi LJ. Is phenytoin contraindicated in patients receiving cranial irradiation? Australas Radiol. 1995;39:42-46.

7.Cockey GH, Amann ST, Reents SB, Lynch JW, Jr. Stevens-Johnson syndrome resulting from whole-brain radiation and phenytoin. Am J Clin Oncol. 1996;19:32-34.

8.Duncan KO, Tigelaar RE, Bolognia JL. Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital. J Am Acad Dermatol. 1999;40:493-496.

9.Khafaga YM, Jamshed A, Allam AA, et al. Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy. Acta Oncol. 1999;38:111-116.

10.Micali G, Linthicum K, Han N, West DP. Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies. Pharmacotherapy. 1999;19:223-227.

11.Eralp Y, Aydiner A, Tas F, Saip P, Topuz E. Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation. Am J Clin Oncol. 2001;24:247-350.

12.Trent JT, Bowes LE, Romanelli P, Kerdel FA. Toxic epidermal necrolysis of the scalp following anticonvulsant use and cranial irradiation. J Cutan Med Surg. 2001;5:475-478.

13.Maldonado N, Tello J, Garcia-Baquero E, Castano A. Anticonvulsant hypersensitivity syndrome with fatal outcome. Eur J Derm. 2002;12:503-505.

14.Aguiar D, Pazo R, Duran I, et al. Toxic epidermal necrolysis in patients receiving anticonvulsants and cranial irradiation: a risk to consider. J Neurooncol. 2004;66:345-350.

15.Ahmed I, Reichenberg J, Lucas A, Shehan JM. Erythema multiforme associated with phenytoin and cranial radiation therapy: a report of three patients and review of the literature. Int J Dermatol. 2004;43:67-73.

16.Oner Dincbas F, Yoruk S, Demirkesen C, Uzel O, Koca S. Toxic epidermal necrolysis after cranial radiotherapy and phenytoin treatment. Onkologie. 2004;27:389-392.

17.Whorl S, Loewe R, Pickl W, Stingl G, Wagner S. EMPACT syndrome. Dtsch Dermatol Ges. 2005;3:39-43.

18.Aydin F, Cokluk C, Senturk N, Aydin K, Canturk MT, Turanli AY. Stevens-Johnson syndrome in two patients treated with cranial irradiation and phenytoin. J Eur Acad Dermatol Venereol. 2006;20:588-590.

19.Fernandez FA, Pintor E, Quesada R, Garces FJ. Toxic epidermal necrolysis induced by phenytoin and whole brain radiotherapy. Actas Dermosifiliogr. 2007;98:483-485.

20.Barbosa LA, Teixeira CR. Erythema multiforme associated with prophylactic use of phenytoin during cranial radiation therapy. Am J Health Syst Pharm. 2008;65:1048-1050.

21.Ranu H, Pang S. Toxic epidermal necrolysis in a breast cancer patient treated with whole brain radiotherapy and phenytoin: should phenytoin have been used? Hong Kong J Dermatol Venereol. 2008;16:155-159.

22.Sarma N. Stevens-Johnson Syndrome and toxic epidermal necrolysis overlap due to oral temozolomide and cranial radiotherapy. Am J Clin Dermatol. 2009;10:264-267.

23.Aydogan K, Vatansever S, Adim SB, Saricaoglu H. Empact syndrome: a case report and review of the literature. Int J Dermatol. 2010;49:945-949.

24.Kandil AO, Dvorak T, Mignano J, Wu JK, Zhu JJ. Multifocal Stevens-Johnson syndrome after concurrent phenytoin and cranial and thoracic radiation treatment, a case report. Radiat Oncol. 2010;5:49.

25.Bilgili SG, Calka O, Karadag AS, Burakgazi AZ. EMPACT syndrome. Cutan Ocul Toxicol. 2011;30:328-330.

26.Fabbrocini G, Panariello L, Pensabene M, et al. EMPACT syndrome associated with phenobarbital. Dermatitis. 2013;24:37-39.