Specific Immunotherapy in Atopic Dermatitis Four- Year Treatment in Different Age and Airborne Allergy Type Subgroups

Transcription

1 At Dermtovenerol Crot 2006;14(4): CLINICAL ARTICLE Speifi Immunotherpy in Atopi Dermtitis Four- Yer Tretment in Different Age nd Airorne Allergy Type Sugroups Mgdlen Czrnek-Operz, Wojieh Silny Deprtment of Dermtology nd Allergi Diseses Dignosti Center, University of Medil Sienes, Poznń, Polnd Corresponding uthor: Professor Mgdlen Czrnek-Operz, MD, PhD 49 Przyyszewskiego Str Poznń, Polnd Reeived: My 16, 2005 Aepted: Mrh 10, 2006 SUMMARY Atopi dermtitis (AD) is ommon inflmmtory disese involving the skin nd frequently other orgns nd systems suh s respirtory system. The reently reognized topi nture of the skin inflmmtion in AD hs rised growing interest in the tretment with llergenspeifi immunotherpy (SIT). In this study, the effiy of SIT ws evluted in group of 37 AD ptients ged 5-44 yers: 14 llergi to house dust mites (HDM), 17 to grss pollen llergens, nd 6 llergi to grss nd mugwort pollen llergens. IgE-medited irorne llergy ws well doumented in ll ses. SIT ws performed with Novo Helisen Depot llergy vines of pproprite omposition. Control group inluded 29 ptients with AD nd onfirmed IgE-medited irorne llergy to nlogous llergens: HDM, 14 ptients; grss pollen llergens, 11 ptients; nd grss nd mugwort pollen llergens, 4 ptients. Conventionl methods of AD tretment were used in the ontrol group. Clinil evlution of ptients ws performed with W-AZS index fter 12, 24, 36 nd 48 months of therpy. SIT ws found to e n effiious nd sfe method of tretment for seleted ptients with AD nd IgE-medited irorne llergy. The effiy of this therpeuti method ws signifintly higher thn tht reorded y onventionl methods used in the ontrol group in ll 3 ge sugroups nd ll 3 types of irorne llergy (HDM, grss pollen, nd grss nd mugwort pollen). It is onluded tht SIT my e highly promising method of ontrolling skin inflmmtion in AD with the potentil to prevent the development of AD into respirtory llergy. KEY WORDS: topi dermtitis; llergy; speifi immunotherpy; tretment INTRODUCTION Aording to the definition presented t the Seond Interntionl Consensus Conferene on Atopi Dermtitis (ICCAD II) (1), topi dermtitis (AD) is pruriti, inflmmtory, hroni skin disese tht typilly egins in erly hildhood nd my ontinue to reur s dult disese. While vrious ptterns of expression my eventully e shown to represent different geneti sutypes, 230

2 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): there is no urrent distintion etween dult nd hildhood topi dermtitis. The following set of onsensus sttements on AD represent our updted knowledge (2): AD is ommon hroni inflmmtory skin disese. It is hrterized y intense ithing, dry skin, inflmmtion nd relpses, nd it uses physil nd emotionl distress in ptients nd their fmilies. AD is often fmilil nd frequently ssoited with sthm, food llergy, llergi rhinitis, nd reurrent skin infetions. Trigger ftors suh s stress, irritnts, miroes nd llergens should e identified nd voided. In the sene of ure, erly effetive tretment should e initited to redue the signs, symptoms nd reurrenes, nd to prevent progression of the disese. Emphsis should e put on long-term ontrol rther thn just retive mngement of relpses. Topil ortiosteroids provide effetive, ute ontrol ut provoke sfety onerns when used ontinuously; furthermore, ptients do not lwys use steroids s presried y their physiins. There is need for sfe, effetive therpy for erly ontrol nd long-term mintenne. The new lss of topil lineurin inhiitors my fulfill this unmet need. Tretment of AD is still hllenge for physiins nd in mny ses the disese is poorly ontrolled. Topil ortiosteroids re responsile for vrious side effets, reound phenomenon, while the lk of onfidene in steroid sfety lso dversely ffets ompline nd undertretment of hildren with AD. Systemi tretment is ssoited with potentilly severe dverse effets nd is generlly not reommended exept s lst resort (3). Phototherpy is inonvenient nd my rry risk of future skin ners or/nd photoging. Immunosuppressnts suh s ylosporine or zthioprine require pproprite monitoring euse of their potentil effets on orgn toxiity, inresed risk of infetions nd possily lymphom, nd my interfere with immuniztion in hildhood. And finlly llergen-speifi immunotherpy (SIT) should e mentioned, euse linil enefit of this method hs een shown in the tretment of AD ptients (2). SIT in seleted ses of AD ptients with IgE-medited irorne llergy ws one of our min interests for the lst few yers. In our opinion SIT fulfills therpeuti ojetives for AD euse it: redues the signs nd symptoms of the disese, prevents or redues reurrenes, provides long-term mngement y preventing exertions, nd modifies the ourse of the disese. This pper presents our results on SIT performed s n open study over 4-yer period, nd disusses differenes reorded in ptient sugroups divided ording to ge nd type of irorne llergy. It is prt of omplex projet on SIT in AD, whih inludes doule lind pleo ontrolled 12-month study. Mteril nd methods The study inluded two groups of AD ptients: SIT group of 37 ptients (25 femle nd 12 mle, ge rnge 5-44, men ge 18 yers) with moderte to severe disese tivity evluted y W-AZS index: 94.5±39.7 points (4,5) (Tles 1 nd 2). All ptients hd exorited skin lesions with intensive pruritus. IgE-medited irorne llergy ws onfirmed in ll ptients (linil evlution, skin prik tests with erollergens, totl IgE, nd IgE ginst erollergens); 17 ptients were llergi to grss pollen llergens, 6 ptients to grss nd mugwort pollen llergens, nd 14 ptients to house dust mite llergens (Dermtophgoides (D.) pteronyssinus nd Dermtophgoides (D.) frine). This group of ptients were dministered SIT with Novo-Helisen Depot vines over 4-yer period. Control group onsisted of 29 AD ptients (19 femle nd 10 mle, ge rnge 5-41, men ge 17 yers) with moderte to severe disese tivity s ssessed y W-AZS index: 86.9±24.0 points. Before therpy, there ws no signifint etween group differene in the linil tivity of AD. Control group ptients met ll the riteri for SIT ut did not wnt to reeive llergy vintion. Eleven of these ptients were llergi to grss pollen llergens, four to grss nd mugwort pollen llergens, nd 14 to house dust mite llergens (D. pteronyssinus nd D. frine). In this group of ptients onventionl methods of tretment were used during the 4-yer period. Speifi immunotherpy Novo-Helisen Depot llergy vines were used in the tretment of the SIT group. The omposition 231

3 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): of vines ws seleted individully ording to the linil nd llergologil hrteristis of ptients. The following llergy vines were used: 1. grss pollen llergens 100% in 17 ptients 2. grss pollen llergens 80% nd mugwort pollen llergens 20% in 6 ptients 3. house dust mite llergens D. pteronyssinus 50% nd D. frine 50% in 14 ptients Novo-Helisen Depot llergy vines were dministered perennilly y the lssi suutneous route in ll three types of irorne sensitiztion. The following onentrtions of llergen extrts were used: onentrtion 1, 50 TE/mL onentrtion 2, 500 TE/mL onentrtion 3, 5000 TE/mL (TE=therpeuti unit) SIT ws performed ording to the lssi protool, strting with 0.05 ml of onentrtion 1 (50 TE/mL). Injetions were then dministered every 7-14 dys with grdully inresing doses of llergen extrts to the mintenne dose (1 ml of onentrtion 3, 5000 TE/mL). Finlly, the mintenne dose ws repeted every 4 weeks for the totl SIT period of 4 yers. The totl dose dministered throughout this period ws pproximtely TE (47000TE per yer). In se of sesonl sensitiztion during the pollintion seson the dose ws redued ording to linil piture (y 20%-50% of the plnned dose). Conventionl tretment onsisted of ntihistmini drugs (genertion I nd II), ntipruriti gents, nti-inflmmtory gents, topil steroids, moisturizing nd gresing gents. Clinil ssessment ws performed efore nd fter 12, 24, 36 nd 48 months of tretment in oth study groups. W-AZS index ws used on linil evlution of ptients (Tles 1 nd 2). Tle 1. W-AZS index I EVALUATION OF PRURITUS AND LOSS OF SLEEP IN PATIENTS WITH ATOPIC DERMATITIS. A. PRURITUS EVALUATION: POINTS No pruritus. 0 Pruritus is present: Extensiveness: 1. Single or multiple loliztion of pruritus Extensive pruritus involving whole ody surfe... 6 Frequeny: 1. Short episodes of pruritus - less thn 30 minutes Longlsting pruritus episodes Constnt pruritus... 8 Severity: 1. Srthing is not neessry Srthing is neessry Anxiety nd irrittion used y pruritus 8 B. LOSS OF SLEEP EVALUATION: 1. No loss of sleep Prolems in flling sleep Night wkening used y pruritus Sleeplessness TOTAL ( A + B ). +. = I 232

4 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): Tle 2. W-AZS index II EVALUATION OF EXTENSIVENESS AND SEVERITY OF SKIN INFLAMMATION IN PATIENTS WITH ATOPIC DERMATITIS Extensiveness of skin lesions 1. Fe nd nek 2. Slp nd nuh 3. Trunk (nterior surfe) 4. Trunk (posterior surfe) 5. Right rm 6. Right forerm nd hnd 7. Left rm 8. Left forerm nd hnd 9. Right thigh 10. Right shnk nd foot 11. Left thigh 12. Left shnk nd foot A ( )x1= ( )x1= ( )x4= ( )x4= ( )x1= ( )x1= ( )x1= ( )x1= ( )x2= ( )x2= ( )x2= ( )x2= Severity of skin inflmmtion erythem vesiles rusts liheniztion B edem erosions sling pigmenttion ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = ( )x3 + ( )x3 + ( )x2 + ( ) = A x B 10 TOTAL II Sore extensiveness of skin lesions 0-3: Sore severity of skin inflmmtion 0-3: 0 = not present 0 = not present 1 = 1-10% of skin surfe involved 1 = mild 2 = 11-30% of skin surfe involved 2 = moderte 3 = % of skin surfe involved 3 = severe TOTAL W-AZS : I + II Sttistil nlysis Sttistil evlution ws performed y use of Student s t-test, ANOVA/MANOVA polydimensionl nlysis, Wiloxon test nd Mnn-Whitney U test. For evlution of orreltions, Spermn rnk orreltion oeffiient ws lulted for sttistil signifine. RESULTS Clinil effiy ording to ge sugroups Ptients with AD were divided into three ge sugroups: sugroup 1, hildren ged 5-14 yers (n=16); sugroup 2, ptients ged (n=9); nd sugroup 3, ptients ged >21 (n=12). In the ontrol group, the respetive figures were 14, 5 nd 10. Men vlues of W-AZS sore for prtiulr ge sugroups nd sttistil nlysis of results re presented in Tles 3 nd 4, nd Figure 1. In the SIT ge sugroup 1, the men W-AZS sore deresed from 84.0±39.3 points efore tretment to 5.4±5.2 points fter 48-month therpy. At 24, 36 nd 48 months of tretment, the disese severity deresed signifintly (p<0.001) in omprison with the initil sttus. In the SIT ge sugroup 2, the men vlue of W-AZS sore ws 102.0±38.7 points efore nd 21.2±35.3 points fter 48 months of SIT. A sttistilly signifint linil improvement from the initil sttus ws reorded t 24 months (p<0.05) s well s t 36 nd 48 months (p<0.001) of therpy. In the SIT ge sugroup 3, the men vlue of W-AZS sore ws 102.9±41.1 points efore tretment to derese to 11.2±

5 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): Figure 1. Men vlues of W-AZS sore ±SD in the SIT nd ontrol groups ording to ge groups points fter tretment. The 24-, 36- nd 48-month SIT resulted in signifint linil improvement (p<0.01 t 24 months, nd p<0.001 t 36 nd 48 months). In the ontrol group, ptients ged 5-14 showed men pretretment W-AZS sore of 86.4±28.4 points, whih deresed to 42.2±24.0 points fter 48 months. A signifint improvement ws reorded t 24, 36 nd 48 months of therpy (p<0.001, p<0.01 nd p<0.001, respetively). Ptients ged treted with onventionl methods showed pretretment W-AZS sore of 99.5±21.2 points, whih deresed to 50.6±34.2 points fter 48 months of tretment. A sttistilly signifint differene in the linil sore in omprison with the initil sttus ws only reorded t 48 months of tretment (p<0.05). In the ontrol sugroup ged >21 the linil sore ws s follows 81.3±17.6 points efore nd 52.4±23.8 points t 48 months of onventionl therpy. After 12, 36 nd 48 months of therpy linil improvement ws sttistilly signifint in omprison with the initil sttus (p<0.01, p<0.001, nd p<0.05, respetively). Comprtive sttistil nlysis of linil results otined in the SIT nd ontrol groups is presented in Tle 4. In the 5-14 ge group there ws sttistilly signifint differene in fvor of SIT group fter 12, 24, 36 nd 48 months of tretment (p<0.05 t 12 months, nd p<0.001 t 24, 36 nd 48 months). In the ge sugroup there ws signifint differene in fvor of SIT group fter 24, 36 nd 48 months of therpy (p<0.05). In the >21 ge sugroup signifint differene in fvor of SIT group ws reorded fter 24,36 nd 48 months of tretment (p<0.01 t 24 months, nd p<0.001 t 36 nd 48 months). Clinil effiy ording to type of ir orne llergy Tles 5 nd 6, nd Figure 2 summrize results of tretment with llergy vines nd onventionl methods in AD ptients with different types of IgE-medited irorne llergy. In the SIT group 14 ptients were llergi to HDM llergens (D. pteronyssinus nd D. frine), 17 ptients were llergi to grss pollen llergens, nd 6 ptients were llergi to grss nd mugwort pollen llergens. In ptients llergi to HDM llergens the men vlue of W-AZS sore ws 98.8±44.3 points efore nd 14.7±25.8 points fter 48 months of tretment. There ws signifint differene in the linil sore fter 48 months of SIT in omprison with the initil linil sttus of ptients (p<0.001). In the group of ptients llergi to grss pollen llergens the men vlue of W-AZS sore ws 100.1±34.1 points efore tretment to derese to 9.3±15.9 points t 48 months of therpy. Results of sttistil nlysis were similr to those reorded in the previous group. A signifint differene ws reorded fter 48 months of SIT in omprison with the initil linil sore (p<0.001). In the group of 10 ptients llergi to grss nd mugwort pollen llergens the men vlue of W-AZS sore ws 68.6±39.9 points efore nd 7.9±5.9 points fter 48 months of SIT, yielding sttistilly signifint differene. In the ontrol group, there were 14 ptients llergi to HDM llergens,11 ptients llergi to grss pollen llergens, nd four ptients llergi to grss nd mugwort pollen llergens. In ptients llergi to HDM llergens the men vlue 234

6 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): Tle 3. Men vlues of W-AZS sore in the SIT nd ontrol groups of ptients with AD ording to ge groups Men vlue of W-AZS sore (pts) ± SD SIT group Control group Age (yrs) Age (yrs) 5-14 (n-16) (n-9) > 21 (n-12) 5-14 (n-14) (n-5) >21 (n-10) Before tretment 84.0± ± ± ± ± ±17.6 At 12 months 34.8± ± ± ± ± ±16.1 At 24 months 16.1± ± ± ± ± ±20.8 At 36 months d 10.1± ± ± ± ± ±20.5 At 48 months e 5.4± ± ± ± ± ±23.8 SIT group: ge 5-14 ge ge >21 /; /; /d; d/e (NS) /; /d; /e (p<0.001) /; /; /d; d/e (NS) / (p<0.05) /d; /e (p<0.001) /; /; /d; d/e (NS) / (p<0.01) /d; /e (p<0.001) Control group: ge 5-14 ge ge >21 /; /; /d; d/e (NS) / (p<0.01) /d; /e (p<0.001) /; /; /d; /, /d, d/e (NS) /e (p<0.05) / (p<0.01) /; /, /d, d/e (NS) /d (p<0.001) /e (p<0.05) of W-AZS sore ws 80.1±20.2 points efore nd 45.3±25.8 points fter 4 yers of onventionl tretment. A signifint improvement of the linil sore in omprison with the initil sttus ws reorded t 12 months (p<0.01) nd 48 months (p<0.001) of therpy. In the 11 ptient llergi to grss pollen llergens the men vlue of W-AZS sore ws 94.6±27.6 points efore nd 47.8±27.7 points t 48 months of therpy. After 48 months of lssi tretment there ws signifint improve- Tle 4. Comprtive sttistil nlysis of linil sore (W-AZS) in the SIT nd ontrol group CLINICAL SCORE W-AZS SIT group Control group Sttistil nlysis Age (yrs) Age (yrs) Before tretment At 12 months At 24 months At 36 months At 48 months 5-14 (n=16) (n=9) >21 (n=12) 5-14 (n=14) (n=5) >21 (n=10) Sttistil signifine / p>0.05 / p>0.05 / p>0.05 / p<0.05 / p>0.05 / p>0.05 / p<0.001 / p<0.05 / p<0.01 / p<0.001 / p<0.05 / p<0.001 / p<0.001 / p<0.05 / p<

7 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): Tle 5. Men vlues of W-AZS sore ± SD in ptients with AD treted with SIT nd in ontrol group ording to type of irorne llergy D. pteronyssinus D. frine (n=14) SIT group Control group Grss pollen (n=17) Grss nd mugwort pollen (n=6) D. pteronyssinus D. frine (n=14) Grss pollen (n=11) Grss nd mugwort pollen (n=4) Before tretment 98.8± ± ± ± ± ±25.0 At 12 mo 36.8± ± ± ± ± ±14.6 At 24 mo 18.7± ± ± ± ± ±17.2 At 36 mo d 16.9± ± ± ± ± ±10.4 At 48 mo e 14.7± ± ± ± ± ±22.5 SIT group ptients llergi to HDM llergens - /; /; /d; d/e (NS) - /e (p<0.001) ptients llergi to grss pollen llergens - /; /; /d; d/e (NS) - /e (p<0.001) ptients llergi to grss nd mugwort pollen llergens - /; /; /d; d/e (NS) - /e (p<0.001) Control group ptients llergi to HDM llergens - / (p<0.01) - /e (p<0.001) - /; /d; d/e (NS) ptients llergi to grss pollen llergens - /; /; /d; d/e (NS) - /e (p<0.01) ptients llergi to grss nd mugwort pollen llergens - /; /; /d; d/e (NS) - /e (p<0.05) Tle 6. Results of omprtive sttistil nlysis of the W-AZS linil sore etween SIT nd ontrol groups of ptients with AD Before tretment At 12 months At 24 months At 36 months At 48 months D. pteronyssi nus D. frine (n=14) (n-14) SIT group Grss pollens (n=17) Grss nd mugwort pollens (n=6 ) D. pteronyssi nus D. frine (n-14) Control group Grss pollens (n=11) Grss nd mugwort pollens (n=4 ) Sttistil nlysis Sttistil signifine / p>0.05 / p>0.05 / p>0.05 / p<0.05 / p<0.05 / p>0.05 / p<0.01 / p<0.01 / p<0.05 / p<0.01 / p<0.001 / p<0.05 / p<0.01 / p<0.001 / p<

8 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): Figure 2. Men vlue of W-AZS sore ±SD in ptients with AD treted with SIT nd in the ontrol group ording to type of llergy ment of the linil sore in omprison with the initil sore (p<0.01). In the four ptients llergi to grss nd mugwort pollen llergens treted with onventionl methods the men vlue of W-AZS ws 89.8±25.0 points efore nd 51.8±22.5 points fter 48 months of onventionl therpy. In this ptient sugroup sttistilly signifint differene ws reorded etween the initil linil sttus nd the linil sore otined t 48 months of therpy (p<0.05). Comprtive sttistil nlysis in the group of ptients llergi to HDM llergens (Tle 6) reveled sttistilly signifint differene of linil sore in fvor of SIT ptients fter 12, 24, 36 nd 48 months of tretment (p<0.05 t 12 months, nd p<0.01 t 24, 36 nd 48 months). In ptients llergi to grss pollen llergens there ws no signifint differene etween the SIT nd ontrol groups efore tretment, however, signifint differene in fvor of SIT group ws oserved t 12, 24, 36 nd 48 months of therpy (p<0.05 t 12 months, nd p<0.01 t 24, 36 nd 48 months). In ptients llergi to grss nd mugwort llergens there ws no signifint etween group differene efore nd fter 12 months of therpy, however, signifint differene in fvor of SIT group ws reorded t 24, 36 nd 48 months of tretment (p<0.05). DISCUSSION The reent viewpoint on AD immunopthogenesis proposes iphsi ytokine expression s model of disese progression from the erly ute to the hroni stge of skin inflmmtion. It seems tht IFNγ/IL-12-dependent TH2 Th1 swith is responsile for sustined AD progression, nd therefore ytokines themselves might e regrded for potentil tretment. Controlled studies hve shown the sfety nd effiy of long-term use of reominnt IFN-γ (rifn-γ) in the tretment of AD (6-8). Sine IFNγ/IL-4 imlne is ommonly epted to e the entrl immune defet in topi llergy, this therpy seems to e very rtionl nd promising. Also onsidering SIT s the only method whih is ple of modifying the nturl ourse of the topi proess y reversing the imlne of Th2/Th1 supopultions, this therpy should e onsidered potentilly enefiil. Although sientifi reserh on SIT hs een performed for nerly entury (9), its results hve only reently nd prtilly een epted (10). One of the resons perhps lies in the met-nlysis tehnique s well s in the sientifi nd sttistil methodology used for vlidtion of SIT effiy (11,12). The ritil differene etween the symptomti nture of phrmologil tretment nd the usl, pthogeni nd preventive nture of SIT should e lerly stressed. The inditions for SIT in llergi rhinitis nd sthm, only limited to ses in whih phrmologil tretment is not dequte to ontrol symptoms, rise the question of the equivlene of therpies (13). Also, disussing the linil effiy of SIT, we se our seletion of studies on the riteri diretly extrpolted from tht of drug trils. DBPC, rndomized study design, oviously provides highest grde evidene for the effiy nd sfety of the investigted drug 237

9 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): tht exerts its tion in short time nd is poorly influened y onfounding ftors (13). Clinil response in se of SIT is time-relted nd generlly long period is required to limit the inflmmtory proess. Therefore, well-designed oservtionl studies should lso e evluted for proper nlysis of the SIT linil effiy, otherwise there is high risk of the result underestimte. The WHO position pper sttes tht SIT for AD is only epted for linil trils, s exlusively two DBPC trils hve een evluted. Aording to our knowledge, there hve een t lest 5 suh trils nd results otined y the uthors re promising (14-18). Therefore, we elieve tht AD ptients with IgE-medited irorne llergy who do not respond to onventionl tretment my e seleted for SIT. This pper present results of linil evlution of SIT performed for 4 yers in seleted ses of AD. We imed to nlyze ny possile differenes ording to ge nd type of irorne llergy. We expeted SIT to e most effetive in youngest AD ptients with higher dptive properties of the immune system. In ft, these hildren presented the lowest men W-AZS sore fter 48 months of SIT; however, the highest sore ws not reorded in the oldest ge sugroup ut in ptients ged (the medium ge group). SIT resulted in grdul nd ontinuous linil improvement in ll three ge sugroups (5-14, nd >21 yers). Clinil improvement ws reorded lredy t 12 months of tretment, ut it did not reh sttistil signifine (ll three sugroups); fter 24, 36 nd 48 months it ws sttistilly signifint. In youngest ptients (ge sugroup 1) the linil sore improved more signifintly fter 24 months of SIT in omprison with the other two ge sugroups nd it ws nother ge-relted differene. In the ptients treted with onventionl methods we lso reorded linil improvement in ll three ge sugroups. In ge sugroup 1 (5-14 yers), linil improvement ws not signifint t 12 months, ut rehed sttistil signifine t 24, 36 nd 48 months. In ge sugroup 2 (15-21 yers) sttistilly signifint linil improvement ws only reorded t 48 months of onventionl tretment. In ge sugroup 3 (>21 yers) linil improvement ws oserved t 12, 36 nd 48 months of therpy in omprison to the initil sore. Therefore, the improvement of linil sttus in the ontrol group ws not s stedy nd ontinuous s in the SIT group. Comprtive sttistil nlysis of the SIT nd ontrol group tretment effiy reveled signifint differene in fvor of SIT ptients in ll ge supopultions. In the youngest ptients this differene ws sttistilly signifint fter 12, 24, 36 nd 48 months of tretment, nd in the other two sugroups it ws signifint fter 24, 36 nd 48 months of tretment. In onlusion, SIT ws more effetive thn onventionl tretment of AD ptients in ll ge sugroups, with the est result in youngest ptients. The hildren ged 5-14 exhiited etter response lredy t 12 months of SIT nd the est linil sore t the end of the study. Another prmeter tken into onsidertion in terms of linil effiy of SIT ws the type of IgE-medited irorne llergy (HDM, grss pollen, grss nd mugwort pollen). The ptients llergi to HDM treted with llergy vines (Novo- Helisen Depot llergy vines: D. pteronyssinus 50%, D. frine 50%, n=14) showed linil improvement lredy t 12 months of SIT, however, signifint differene ws reorded t 48 months of tretment. In the group of ptients llergi to grss pollen llergens treted with llergy vines nd those llergi to grss nd mugwort pollen llergens linil improvement ws grdul nd ontinuous, nd ws oserved lredy t 12 months of SIT, to reh sttistil signifine t 48 months of tretment. The only exeption ws oserved in the group of ptients llergi to grss pollen llergens during the lst yer of tretment, when their men W-AZS sore slightly inresed (y 1.7 points). The results otined in the ontrol group were somehow different in ll three supopultions. In the ptients llergi to HDM llergens linil improvement ws signifint lredy t 12 months of tretment nd then t 4 yers of therpy, lthough the finl linil sore in the ontrol group ws muh worse in omprison with the SIT group (45.3 vs 14.7). The ptients llergi to grss pollen llergens nd those llergi to grss nd mugwort pollen llergens exhiited signifint linil improvement only fter 48 months of tretment. Comprtive sttistil nlysis of the SIT nd ontrol groups yielded sttistilly signifint differene in fvor of SIT group fter 12 months of therpy in the ptients llergi to HDM nd those llergi to grss pollen llergens. After 24, 36 nd 48 months of tretment sttistilly signifint differene in fvor of SIT group ws reorded in ll three llergy type supopultions (ptients llergi to HDM, to grss pollen llergens, nd to grss nd mugwort pollen llergens). It is therefore onluded tht SIT is more effetive thn 238

10 Czrnek-Operz nd Silny At Dermtovenerol Crot Speifi immunotherpy in topi dermtitis 2006;14(4): lssi tretment of AD irrespetive of the type of IgE-medited irorne llergy. However, in se of the most omplex type, grss nd mugwort pollen llergy, sttistilly signifint differene in W-AZS sore in omprison with the ontrol group ws oserved lter thn in the other two llergy type supopultions. Allergen speifi immunotherpy hs een reognized y the WHO s the only therpeuti modlity tht n ffet the nturl ourse of llergi diseses (10,19) euse of the proven linil effiy nd speifi immune hnges thus indued. At Deprtment of Dermtology nd Allergi Diseses Dignosti Center of the University of Medil Sienes in Poznń, this method of tretment hs een refully studied in AD ptients for yers (20-28). In our opinion, SIT my e n effetive nd promising method of tretment in seleted ptients with AD nd IgE-medited irorne llergy. This type of systemi therpy is dministered to orret the immune derngement underlying AD nd should e onsidered s one of the elements of omplex therpeuti strtegies in AD. Referenes 1. Hnifin J, Surt JH. Proeedings of the Interntionl Consensus Conferene on Atopi Dermtitis. Rome, Itly, Novemer 5-6, J Am Ad Dermtol 2001;45: S Ellis C, Luger T. Interntionl Consensus Conferene on Atopi Dermtitis II (ICCAD II). Chirmn s introdution nd overview. Br J Dermtol 2003;148: Sidury R, Hnifin JM. Systemi therpy of topi dermtitis. Clin Exp Derm 2000;25: Silny W, Czrnek-Operz M, Gołęk E, Silny P. W-AZS new soring index for ptients with topi dermtitis. Przegl Dermtol 1999;86: Czrnek-Operz M, Btor-Wegner M, Silny W. Atopy pth test retion to irorne llergens in the dignosis of topi dermtitis. At Dermtovenereol Crot 2005;13: Hnifin JM, Shneider LC, Leung DYM, Ellis CN, Jffe HC, Izu AE, et l. Reominnt interferon gmm therpy for topi dermtitis. J Am Ad Dermtol 1993;28: Shneider LC, Bz Z, Zrone C, Zurkowski D. Long-term therpy with reominnt interferon-gmm (rifngmm) for topi dermtitis. Ann Allergy Asthm Immunol 1998;80: Jng IG, Yng JK, Lee HJ, Yi JY, Kim HO, Kim CW, et l. Clinil improvement nd immunohistohemil findings in severe topi dermtitis treted with interferon gmm. J Am Ad Dermtol 2000;42: Noon L, Cnt BO. Prophylti inoultion ginst hy fever. Lnet 1911;1: Bousquet J, Lokey RF, Mlling HJ. WHO position pper. Allergen immunotherpy therpeuti vines for llergi diseses. Allergy 1998;53: Boquete M, Crlld F, Exposito F, Gonzlez A. Preventive immunotherpy. Allergol Immunopthol 2000;28: Sendin I. Evlution of peditri spets of the WHO doument nd met-nlysis of immunotherpy. Allergol Immunopthol 2000;29: Mstrndre F. Immunotherpy in topi dermtitis. Exp Opin Invest Drugs 2001;10: Glover MT, Atherton DJ. A doule-lind ontrolled tril of hyposensitiztion to Dermtophgoides pteronyssinus in hildren with topi ezem. Clin Exp Allerg 1992;22: Leroy BP, Lhpelle JM, Somville MM, Jquemin MG, Sint-Remy JM. Injetion of llergen-ntiody omplexes is n effetive tretment of topi dermtitis. Dermtologi 1991;182: Kufmn HS, Roth HL. Hyposensitiztion with lum preipitted extrts in topi dermtitis: pleo ontrolled study. Ann Allergy 1974;32: Ring J. Suessful hyposensitiztion tretment in topi ezem: results of tril in monozygoti twins. Br J Dermtol 1982;93: Silny W, Czrnek-Operz M. Speifi immunotherpy in the tretment of ptients with topi dermtitis results of doule lind pleo ontrolled study. In press. 239

11 Czrnek-Operz nd Silny Speifi immunotherpy in topi dermtitis 19. Theodoropoulos DS, Lokey RF. Allergen immunotherpy: guidelines, updte nd reommendtions of the World Helth Orgniztion. Allergy Asthm Pro 2000;21: Silny W, Czrnek-Operz M. Speifi immunotherpy in the tretment of topi dermtitis. Alergi Astm Immunol 1999;4 (Suppl 2): Silny W, Czrnek-Operz M. Speifi immunotherpy in the tretment of ptients with topi dermtitis. Rev Fr Alergol 1999;56 (Numero speil): Silny W, Czrnek-Operz M. Possile pplition of speifi immunotherpy in the tretment of topi dermtitis modultion of immune response. Alergi Astm Immunol 2000;5 (Suppl 1): Czrnek-Operz M, Silny W. Speifi immunotherpy in seleted ses of topi dermtitis. Przewodnik Lekrz 2001;3: At Dermtovenerol Crot 2006;14(4): Silny W, Czrnek-Operz M. Atopi dermtitis new methods of tretment. Przewodnik Lekrz 2002;3: Czrnek-Operz M. Speifi immunotherpy in the tretment of ptients with topi dermtitis. Poznń: Poznńskie Zkłdy Grfizne SA, Czrnek-Operz M. Allergy vines in the tretment of topi dermtitis. Int Rev Allergol Clin Immunol 2001;7: Czrnek-Operz M. Totl IgE nd ntigen speifi IgE in ptients with topi dermtitis nd irorne llergy treted with speifi immunotherpy. Int Rev Allergol Clin Immunol 2001;7: Czrnek-Operz M, Silny W, Soiesk M. Serum levels of IFN-γ, IL-2R, IL-4, IL-5 nd IL-10 in the ourse of speifi immunotherpy of ptients with topi dermtitis. Int Rev Allergol Clin Immunol 2001;7:2733. Cover of Svijet mgzine; yer (from the olletion of Mr. Zltko Puntijr) 240