450 Lettersto the Editor
GeneralizedBullous Fixed Drug Eruption after In¯ uenza V accination,Simulating Bullous Pemphigoid
I.GarcõÂa-Doval,E. RosoÂn,C.Feal,C. De laTorre, T. RodrõÂguezand M. J.Cruces Departmentof Dermatology, Complexo Hospitalario de P ontevedra,C /LuoreiroCrespo 2, E-36200,P ontevedra,Spain. E-mail:[email protected] AcceptedOctober 19, 2001.
Sir, Severalcases of bullous pemphigoid appearing shortly after in¯uenza vaccination have been described ( 1±3 ).Inone of thema relapsedeveloped after further vaccination one year later( 3).Toourknowledge, there is no previous description ofotherbullous diseases appearing after in¯ uenza vaccination.
CASE REPORT A90-year-oldwoman was seen with a generalizedbullous eruption.She did not remember su Œeringfrom similar lesions previously.She had hypertension treated for more than one yearwith hydrochlorothiazide and valsartan (Co-diovan â ). Sixweeks before the start of cutaneous lesions, nimodipine (Nimotopâ )andginko biloba ( Tanakene â )hadbeen added toher therapy. In October 2000 she received an in¯ uenza vaccination.She denied intake of paracetamol or any other newdrug. Twelve hours after administration of the in¯ uenza vaccine,she noticed pruritus in her genital area and legs. Twenty-fourhours after the vaccination, well-demarcated erythematousmacules and large bullae appeared on these areas,and later on the trunk, hands and face ( Figs.1 and2 ). Somelesions had a darkercentre. She had oral and genital erosions.Systemic symptoms were absent. Suspecting the diagnosisof bullous pemphigoid, a cutaneousbiopsy was taken,and therapy was started with 30 mgof prednisone. Histologyof a skinlesion showed a prominentsubepidermal bullawith scarce perivascular mixed in¯ ammatory in® ltrates, focalhydropic degeneration of the basal layer, pigmentary incontinence,dyskeratotic keratinocytes with pyknotic nuclei inthe epidermis and papillary dermis, and areas of con¯ uent epidermalnecrosis. Direct and indirect immuno¯ uorescence Fig. 1. Erosions afterthe rupture of largebullae. werenegative. Ten days after its institution, prednisone and therest of hertherapy were withdrawn. Bullae disappeared in systemicsymptoms, the spontaneous resolution in 2 weeks 2weeks,and no new lesions had appeared after 10 months, withoutrecurrence ( butleaving persistent pigmented macules), butresidual pigmented macules persisted. She remained normo- andthe characteristic histology and negative immuno¯ uore- tensiveon alow-sodiumcontent diet. According to themanu- scence.The lack of a historyof previous localized lesions facturer,in¯ uenza vaccine ( Vacunaantigripal Pasteur â ) is an couldbe an argument against this diagnosis. However, in an inactivatedsubunit split vaccine that contains hemagglutinin, oldpatient with some cognitive disturbances minor lesions neuraminidase,and residual internal viral structural proteins, couldeasily remain unnoticed. Moreover, the diagnosis of aswell asthiomersal, formaldehyde, neomycin, phosphate ®xeddrug eruption can be madeon the ® rstepisode ( 4). buŒeredsaline and octoxinol-9. 2000-01serotypes were Generalizedbullous ® xeddrug eruption di Œerential A/Moscow/10/99 (H3N2), A/NewCaledonia /20/99 (H1N1) diagnosisincludes toxic epidermal necrolysis and bullous and B/Beijing/184/93.Standard patch tests, including all the pemphigoid.The ® nding,in some cases, of C3 and IgM components(except for octoxinol-9 ),andpatch test with the depositionalong the basement membrane during the early vaccine``as is’ ’,inpreviously a Œectedskin, gave negative phasesof ® xeddrug eruption, can make the distinction from results. bullouspemphigoid more di cult (5). Temporalcriteria led us to consider in¯ uenza vaccination asthe trigger of this patient eruption. The latent period after DISCUSSION thesupposed trigger for ® xeddrug eruption is characteristically We madethe diagnosis of generalized bullous ® xeddrug veryshort ( 5,6 ).In¯uenza vaccination was the only drug eruptionon thebasis of theclinical picture of well-demarcated startedshortly before the eruption. Taking into account the polycycliclesions a Œectingthe face and mucosae, the lack of severityof her lesions, we consideredit unethical to perform
Acta DermVenereol 81 Lettersto theEditor 451
aprovocationtest. The fact that patch testing was negative is notsurprising, as its sensitivity is low ( 7). Toour knowledge, this is the ® rstdescription of generalized bullous® xeddrug eruption after in¯ uenza vaccination. This di cult diŒerentialdiagnosis should always be taken into accountwhen describing bullous pemphigoid induced by vaccination,especially in relapsing cases.
REFERENCES
1.Fournier B, DescampsV, BouscaratF, etal. Bullous pemphigoid inducedby vaccination.Br JDermatol1996; 135: 153± 154. 2.Lear JT, TanBB, EnglishJS. Bullouspemphigoid following in¯uenza vaccination. Clin ExpDermatol 1996; 21: 392. 3.Downs AM,LearJT, BowerCP, KennedyCT. Doesin¯ uenza vaccinationinduce bullous pemphigoid? A reportof fourcases. Br JDermatol1998; 138: 363. 4.Mahboob A, HaaronTS. Drugscausing ® xeddrug eruptions: a studyof 450cases. Int JDermatol1998; 37: 833± 838. 5.Hindsen M, ChristensenOB, GruicV, LofbergH. Fixeddrug eruption:an immunohistochemical investigation of the acute and healingphase. Br JDermatol1987; 116: 351± 360. 6.Breathnach SM, HintnerH. Adversedrug reactions and the skin. Oxford:Blackwell Science, 1992: 72. 7.Lee AY. Topical provocation in 31 cases of ® xeddrug eruption: changeof causative drugs in 10 years. Contact Dermatitis 1998; 38:258± 260.
Fig. 2. Bullouslesion suggestive of bullouspemphigoid.
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