Acta Derm Venereol 92

213 Letters to the Editor 

© 2012 The Authors. doi: 10.2340/00015555-1238

Journal Compilation © 2012 Acta Dermato-Venereologica. ISSN 0001-5555

The strategy for the specic treatment of toxic epider -al necrlysis (TEN) and Stevens-Jhnsn syndre(SJS) (SJS/TEN verla syndre) is cntrversial (1,2). Iediate withdrawal f ssible triggering drugsis andatry. Surtive treatent in an intensive careunit (ICU) is tial fr detecting and treating cli-catins. The rarity f the disease iedes erfrancef cntrlled treatent studies, and case rerts cn-stitute an alternative surce f infratin, rvidingse evidence fr chice f treatent. We rert herethe case f a 15-year-ld by with SJS/TEN verlawh was treated successfully with granulcyte clny

stimulating factor (G-CSF) (lgrastim, Neupogen®,Agen Eure BV, The Netherlands).

CASE REpoRT

A 15-year-ld by resented with a 4-day histry f 

u-like symptoms, high fever, general malaise and hea-dache. Initially, the headache was treated with ne dsef a cbinatin f acetylsalicylic acid (500 g) andcdeine (10 g), and after 3 days he develed a a-culopapular rash, which appeared rst on the trunk and progressed to the extremities and face. He was admit -ted t hsital and initially treated with an intravenus

antibiotic (cefuroxime) on suspicion that infection wasthe triggering agent. The day after adissin hysicalexamination revealed an ill patient with a symmetricallydistributed spotty, dusky-coloured, erythematous exant-hema on the upper trunk and upper thighs. Flaccid bullaewere noted and Nikolsky’s sign was positive. Bullae onthe affected area were easily extended sideways by light pressure (indirect Nikolsky’s sign). New disseminatedaccid blisters lled with serous liquid appeared duringthe physical examination. There were severe mucosalersins in the ral cavity, but n invlveent f thecnjunctiva and genital ucsa.

A clinical diagnsis f SJS/TEN verla was ade, and

was conrmed with a skin biopsy for frozen and routine histlgy.

Microscopy of detached skin displayed total necrosisof the epidermis, covered by a normal basket weavestratum corneum. A 4-mm punch biopsy from the trunk  just outside the detachment area showed conuent, al -most full-thickness epidermal necrosis, with numerousapoptotic keratinocytes among the remaining basalcells. A sparse lymphocytic inltrate was seen in thedereideral interhase.

Labratry investigatins n adissin included:white bld cell cunt 1.4 109/l; latelet cunt 66×109/l;C-reactive rtein (CRp) 15 g/l; albuin 30 g/l. Bld

cultures and serological tests for Herpes simplex virus,Cytegalvirus, and Estein Barr virus were negative.Chest X-ray and echcardigra results were withinnral liits.

Leukocytes decreased to 0.9 109/l the next day andthe atient was transferred t the ICU. The calculated

SCORTEN (SCORe of Toxic Epidermal Necrosis) scorewas 1, and the hsital rtality rate was estiated as3.2% (3).

The patient was also classied using standard severityf illness scring systes after adissin t the ICU,and was fund t have an Acute physilgy and Chrnic

Health Evaluation (APACHE II) score of 20 (a score between 0 and 71, where a higher scre ilies severe

disease and higher risk of death) as well as a SimpliedAcute physilgy Scre (SApS II) f 32 (which rvi-

des an estimate of the risk of death without knowing thediagnosis) (4, 5). During the patient’s stay in the ICUhe develed dysnea (chest X-ray shwed bilateral

 pulmonary inltrates) necessitating non-invasive ven-tilatin. The atient was als lyuric and hytensive

and required large quantities of intravenous uids aswell as infusin f nradrenaline.

The detached skin was left in place and a neutralcrea was alied t the erded areas, which werecvered with nn-adherent bandage aterial.

Intensive care anageent was rvided in ateerature-cntrlled envirnent (32ºC) and the

only specic drug initiated immediately to supplementantibiotics was lgrastim, given over a 3-day period ata daily dose of 5 µg/kg subcutaneously.

The atient was treated in an asetic anner andnursed n an air attress. parenteral nutritin was gi-ven. Eideral detachent rgressed t 25% f theskin surface, and dusky red macular erythema affected70–80% f the bdy surface area. prgressin ceased

within 1 day after starting treatment with lgrastim.The antibitic was discntinued ne day after treatentwith G-CSF was initiated. The tie between the startof development of skin lesions and the maximum levelof skin detachment was 4 days.

The atient was discharged fr the ICU at day 7after admission, with almost complete skin re-epithe -

lialization, and discharged without complications after 13 days.

Successful Treatment of Toxic Epidermal Necrolysis/Stevens-Johnson Syndrome Overlap with

Human Granulocyte Colony Stimulating Factor: A Case Report

Kristine A. Pallesen1, Sian Robinson2, Palle Toft2 and Klaus E. Andersen1  Departments of 1 Dermatology and Allergy Centre and 2 Anaesthesia & Intensive Care, Odense University Hospital, University of Southern Denmark, DK-

5000 Odense C, Denmark. E-mail: Kristine.appel.uldall.pallesen@regionsyddanmark.dk 

 Accepted June 17, 2011.

Included in the theme issue:

 ADVERSE DRUG REACTIONS 

 Acta Derm Venereol 2012; 92: 193–220 

 

214  Letters to the Editor 

DISCUSSIoN

The cause of the patient’s SJS/TEN overlap is unknown.The single dse f a cbinatin f acetylsalicylic acidand cdeine was cnsidered t be an aetilgical factr, but both drugs also have a high risk for confounding byindication, since they are used either to treat the rstsyts f the disease itself, r an infectin whichay be the cause f the disease (6, 7).

TEN and SJS/TEN verla are rare, acute and -tentially fatal diseases, which are st cnly

drug-induced. There is no specic treatment, except for standard surtive care in the ICU. Active treatentwith cyclsrin r intravenus iunglbulin wascnsidered initially, but we were surrised by the raid

improvement within 24 h of the introduction of lgrastim,and decided t withhld suleentary treatent. Neutraenia is crrelated with a r rgnsis in

TEN (8). Therefre, the atient was treated with G-CSF.which appears to accelerate the re-epithelialization. Themechanism is not known. Delayed re-epithelializationhas been observed in GM-CSF “knock-out mice” com- ared with wild tyes (9).

Endogenous G-CSF is produced by monocytes, - brblasts and endthelial cells. In the bne arrw, itregulates the rductin f neutrhils (10) and inducesiuntlerance by activating CD4+ CD 25+ regulatry Tcells (Tregs) fr the bne arrw. This sees t reventfurther tissue daage and facilitate faster recvery (9).

In the case described here the white bld cell cuntrecvered t a nral level the day after startingtreatment with lgrastim, and re-epithalialization wascleted after 7 days. The fast recvery seen in this patient was striking and may encourage a controlleden trial based n a clear rtcl, as has been dnefr cyclsrin and intravenus iunglbulin in thetreatent f TEN (11, 12).

ACkNoWLEDGEmENT

The authors thank Dr Ole Clemmensen, Department of Patholo-gy, Odense University Hospital, for reading the skin biopsies.

The authors declare no conflict of interest.

REFERENCES

Paquet P, Piérard GE. New insights in toxic epidermal1.

necrolysis (Lyell’s syndrome): clinical considerations, athbilgy and targeted treatents revisited. Drug Saf 2010; 33: 189–212.

Harr T, French LE. Toxic epidermal necrolysis and Stevens-2.Jhnsn syndre. orhanet J Rare Dis 2010; 5: 39.Bastuji-Garin S, Fuchard N, Bertcchi m, Rujeau JC,3.

Revuz J, Wolkenstein P. SCORTEN: a severity-of-illnessscore for toxic epidermal necrolysis. J Invest Dermatol2000; 115: 149–153.knaus WA, Draer EA, Wagner Dp, Zieran JE.4.APACHE I: a severity of disease classication system. CritCare med 1985; 13: 818–829.Le Gall JR, Lemeshow S, Saulnier F. A new simplied acute5. hysilgy scre (SAp II) based n a Eurean/Nrth Ae-rican ulticenter study. JAmA 1993; 270: 2957–2963.Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss Y,6.Bork K, et al. ALDEN, an algorithm for assessment of drugcausality in Stevens-Johnson syndrome and toxic epidermalnecrlysis: carisn with case-cntrl analysis. Clinpharacl Ther 2010; 88: 60–68.

Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S,7.

Bouwes Bavinck JN, et al. Stevens-Johnson syndrome andtoxic epidermal necrolysis: assessment of medication riskswith emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Deratl 2008; 128: 35–44.

Kalyoncu M, CimUsit G, Cakir M, Ökten A. Toxic epider -8.al necrlysis treated with intravenus iunglbulinand granulcyte clny-stiulating factr. Indian pediatrics2004: 41: 392–395.Sica-Chapman AD, Williams G, Soni N, Bunker CB.9.Granulocyte colony-stimulating factor in toxic epidermalnecrlysis (TEN) and Chelsea & Westinster TEN rtcl.Br J Deratl 2010; 162: 860–865.Waller CF, Brnchud m, mair S, Challand R. phara-10.cokinetic proles of a biosimilar lgrastim and Amgenlgrastim: results from a randomized, phase I trial. AnnHematol 2010; 89: 927–933.Valeyrie-Allanore L, Wolkenstein P, Brochard L, Ortonne11.

 N, Maître B, Revuz J, et al. Open trial of ciclosporin treat -

ment for Stevens-Johnson syndrome and toxic epidermalnecrlysis. Br J Deratl 2010; 163: 847–853.

Bachot N, Revuz J, Roujeau JC. Intravenous immunoglo -12.

 bulin treatment for Stevens-Johnson syndrome and toxiceideral necrlysis: a rsective nncarative studyshowing no benet on mortality or progression. Arch Der -atl 2003; 139: 33–36.

 Acta Derm Venereol 92