STUDII CLINICE ªI EXPERIMENTALE EXPERIMENTAL AND …bacteriilor (Propionilbacterium acnes) dezvoltate în mediul anaerob, intrafolicular ce întreþin inflamaþia prin compuºii de

17

STUDIU RANDOMIZAT COMPARATIV AL EFICACITÃÞIIªI TOLERANÞEI UNUI TRATAMENT TOPICANTIINFLAMATOR, SEBOREGULATOR ªI

ANTIBACTERIAN LOCAL (CONÞINÂND ACID SALICILIC,ZINC, 5-ALFA AVOCUTA), ASOCIAT CU UN ANTIBIOTICTOPIC (METRONIDAZOL), PE SUBIECÞI PREZENTÂND

ACNEE VULGARÃ, FORME UªOARE ªI MODERATE

RANDOMIZED COMPARATIVE TRIAL EVALUATING THEEFFICACY AND TOLERANCE OF A TOPICAL ANTI-

INFLAMMATORY AND ANTIBACTERIALSEBOREGULATOR (CONTAINING SALICYLIC ACID +

ZINC + 5 ALPHA AVOCUTA), ASSOCIATING A TOPICALANTIBIOTIC (METRONIDAZOLE), ON SUBJECTS WITH

MILD TO MODERATE ACNE VULGARIS

AURA VLÃDUÞI*

Rezumat

Introducere: Acneea vulgarã implicã o dereglare asecreþiei de sebum controlatã androgenic, cu apariþia decomedoane, ce ulterior dezvoltã o reacþie inflamatorie prinacumularea compuºilor ce alcãtuiesc sebumul ºi abacteriilor (Propionilbacterium acnes) dezvoltate în mediulanaerob, intrafolicular ce întreþin inflamaþia prin compuºiide metabolism propriu. Este deci utilã o abordare triplã, descãdere a secreþiei de sebum, asociatã cu o diminuare ainflamaþiei dar ºi cu eliminarea suprainfecþiei bacteriene.

Summary

Background: Acne vulgaris involves a disorder of

androgenic controlled sebum secretion, leading to

appearance of comedons, which then develop an

inflammatory response through accumulation of

compounds forming the sebum and of bacteria

(Propionilbacterium acnes) developed in anaerobic

environment, maintaining intrafollicular inflam-mation by

their metabolic compounds. A triple approach is therefore

* Serviciul de Dermatologie- Ambulatoriul de Specialitate al Spitalul Clinic “C.F. Witting”,Bucureºti, RomâniaDermatology Clinic – Specialty Ambulatory of the Clinic Hospital « C.F.Witting » Bucharest, Romania.

STUDII CLINICE ªI EXPERIMENTALEEXPERIMENTAL AND CLINICAL STUDY

18

DermatoVenerol. (Buc.), 57: 17-41

Introducere

Acneea vulgarã este o afecþiune limitatã strictla nivelul foliculului pilosebaceu. Glandelesebacee din acnee au dimensiuni foarte mari.Sebumul este vital pentru menþinerea echilibruluitenului ºi pãrului, deoarece le protejazã dedeshidratare excesivã ºi agresiunea agenþiloriritanþi. Hiperseboreea poate fi cauzatã de factoriinterni [1] (dezechilibrul hormonal):

– premenstrual la fete [2];– rolul hormonilor androgeni în severitatea

acneei la femei adulte [3];– legãtura dintre acneea vulgarã la femei ºi

prezenþa ovarelor polichistice [4,5] sau – externi (temperaturi crescute, poluare...).

Background

Acne vulgaris is a disease strictly limited tothe pilosebaceous follicle. Sebaceous glands ofacne become very large. Sebum is vital tomaintain balance of skin and hair, as it protectsfrom dehydration and excessive aggressionirritants.

Hiperseboreea can be caused by internalfactors [1] (hormonal imbalance):– premenstrual on girls [2]– the role of androgens in acne severity inadult women [3]– the link between acne vulgaris inwomen and the presence of polycysticovarian [4,5] or

– external (high temperatures, pollution ...).

Obiectiv: A fost evaluatã comparativ eficacitatea ºitoleranþa unui tratament topic constând în substanþeantiinflamatoare, antibacteriene ºi seboregulatoare (acidsalicilic, Zinc, acid glicolic, 5-alfa avocuta), asociate cu unantibiotic topic, metronidazolul.

Metode: Studiul s-a realizat unicentric, randomizat,cu evaluare comparativã a douã zone simetrice pe 30 depacienþi cu acnee vulgarã forme uºoare ºi moderate, timp de12 sãptãmâni. 15 pacienþi au fost trataþi pe jumãtate de faþãcu gel de curãþare (acid salicilic 1%, zinc 0.5%) ºi gelseboregulator ºi antiinflamator (acid glicolic 6.00%, zinc1%, 5 alfa avocuta 1%), iar pe cealaltã jumãtate de faþã cuo cremã neutrã (Placebo); ceilalþi 15 pacienþi au fost trataþipe jumãtate de faþã cu asocierea topicã gel de curãþare + gelseboregulator antiinflamator + metronidazol, iar pe cealaltãjumatate de faþã cu cremã neutrã (Placebo).

Rezultate: Cel mai bun rãspuns s-a obþinut prinutilizarea celor trei topice asociate: gel de curãþare + gelseboregulator antiinflamator + metronidazol (80% dintrepacienþi au avut rezultate dupã primele 4 sãptãmâni ºi 20%dupã 8 sãptãmâni de tratament) faþã de cei trataþi cu gel decurãþare + gel seboregulator antiinflamator: 13% dupã 4sãptãmâni, 20% dupã 8 sãptãmâni ºi 67% dupã 12sãptãmâni de tratament sau mai mult).

Concluzii: Asocierea metronidazolului oferã rezultatemai rapide în acneea vulgarã, pacientul devenind maioptimist, mai încrezãtor ºi mai rãbdãtor în a duce totul labun sfârºit.

Cuvinte cheie: Acnee, hiperseboree, acid glicolic, zinc,alfa avocuta, metronidazol.

useful, to decrease the sebum secretion, the inflammationand also the elimination of bacterial superinfection.

Objective: To evaluate the efficiency of topicalsubstances consisting in antiinflammatory, antibacterialand seboregulative effect (Salicylic Acid-Zinc-GlycolicAcid-5 Alfa Avocuta), associated with a topical antibiotic,metronidazole, versus placebo (a neutral cream).

Methods: Unicentric, randomized, comparative trial,evaluating two symmetrical areas on 30 patients with mildto moderate acne vulgaris. First group of 15 patients weretreated on half face with cleansing gel (1% Salicylic Acid,Zinc 0.5%) and anti-inflammatory and seboregulator Gel(Glycolic Acid 6%, Zinc 1%, 5 Alfa Avocuta1%), versus aneutral cream on the other half of the face. The other groupof 15 patients were treated with the combination of a topicalcleansing gel +Seboregulator and antiinflamatory gel +Metronidazole on half face versus Placebo (neutral cream)on the other half.

Results: The best response was obtained by using allthree topicals in association: cleaning gel (Salicylic Acid1%, Zinc 0.5%) + seboregulator anti-inflammatory gel(6.00% Glycolic Acid, Zinc 1%, 5 Alfa Avocuta 1%) +Metronidazole. Patients treated this way reacted positivelyfaster (80% after the first 30 days and 20% after 60 days oftreatment) than those treated with cleansing gel +seboregulator and anti-inflammatory gel (27% after 60days and 73% after 90 days of treatment).

Conclusions: A more complex topical treatmentassociating Metronidazole gives faster results in acnevulgaris, and the patient become more optimistic, moreconfident and more patient to carry it all to an end.

Keywords: acne, seborhea, glicolic acid, zinc, alfaavocuta, metronidazole.


19


Glandele sebacee, bine vascularizate, au oactivitate predominant controlatã de androgeni[6, 7, 8]. Enzima numitã 5 α-reductazã meta-bolizeazã testosteronul în dihidrotestosteron(DHT), un puternic androgen, la nivelul pielii [9].DHT format acþioneazã asupra folicululuipilosebaceu crescând dimensiunea glandelorsebacee ºi secreþia acestora. Seboreea precedeinstalarea bolii ºi este prezentã atât la nivelul feþeicât ºi a scalpului.

Boala debuteazã printr-o acnee comedogenã[10], la început microcomedoane, apoi come-doane închise, care apoi se lãrgesc ºi devincomedoane deschise [11]. Papulele ºi pustulelereprezintã leziuni secundare de tip inflamator[12,13] care apar ulterior comedonului, fie el ºi dedimensiuni microscopice. Unii pacienþi rãmân înstadiul comedogen de debut, alþii evolueazã sprestadii avansate prezentând atât comedoane cât ºileziuni secundare inflamatorii [12] asociate.Bacteriile joacã un rol subtil în patogeneza acneei[14, 15] ele fiind prezente la nivelul come-doanelor. Dintre aceste, cel mai important rolrevine lui Propionilbacterium acnes [16] care s-adovedit a fi implicat clar în aceastã afecþiune [17],acesta fiind gram pozitiv microaerofil [18] cecreºte cel mai bine în conditii strict anaerobe, deciintrafolicular, folosind sebumul drept nutrient. Elcontribuie la formarea comedoanelor producandsubstanþe care duc la ruptura acestora [19].Apariþia comedoanelor este precedatã deaglomerarea Propionilbacterium acnes la nivelulcanalului folicular. Acesta elibereazã o lipazãdeterminand apariþia acizilor graºi liberi dintrigliceride, foarte comedogenici, determinândreacþia inflamatorie de la nivelul folicululuipilosebaceu generând iritarea ºi distrugereaepitelului folicular. Sebumul revãrsat peri-folicular produce reacþie inflamatorie. Propionil-bacterium acnes produce substanþe toxice careacþioneazã ºi ele asupra epitelului folicular,ducând la ruptura acestuia; aceste proteaze,lipaze [20], fosfataze, neuraminidaze suntimplicate în mecanismul inflamator de tipulhistaminei sau interleukinelor [21, 22]. Propionil-bacterium acnes produce de asemenea porfirinecare pot fi uºor vizualizate la nivelul foliculilorpilosebacei cu pori mari având un aspectfluorescent sub lumina lãmpii WOOD. Foliculiiintens colonizaþi au o fluorescenþã caracteristicã,

Sebaceous glands, supplied by blood, arepredominantly controlled by androgen activity [6,7,8].5 α-reductase enzyme metabolize testosterone todihydrotestosterone (DHT), a potent androgen ofthe skin [9]. DHT acts on the pilosebaceousfollicle increasing the size of sebaceous glandsand their secretion. Seborrhea occures before theonset of the condition and is present on the faceand scalp.

The disease begins as a comedogenic acne[10], first with microcomedones, then closedcomedones, which then become enlarged andeven open comedones [11]. Papules and pustulesdevelop as secondary inflammatory lesions [12,13]. Some patients remain in early comedogenicstage, others evolve to advanced stages showingboth comedones and associated inflammatorylesions [12]. Bacteria play a subtle role in thepathogenesis of acne [14.15], and is prooved toexist inside comedones. Among these, the mostimportant role is being held by Propionil-bacterium acnes [16] which is clearly involved inthis disease [17], by being a gram positivemicroaerophilic [18] and growing under strictlyanaerobic environment, using intrafolicularsebum as a nutrient. He contributes to theformation of comedones producing substancesleading to their rupture [19].

The appearance of comedones is preceded bythe localization of Propionilbacterium acnes inthe follicular duct. It releases a lipase causingreleasing fatty acids from triglycerides, verycomedogenic, and causing inflammation of thefollicle, leading to further irritation anddestruction of pilosebaceous follicule andsurrounding skin. Sebum produces perifolicularinflammation. Propionilbacterium acnes pro-duces toxic substances that act on skin andfollicules leading to its rupture; these proteases,lipases [20], phosphatases, neuraminidases areinvolved in the inflamatory mechanism ofhistamine or interleukins type [21. 22]. Propionil-bacterium acnes also produces porphyrins whichcan be easily viewed on the large pore pilosebaceifollicles by looking at the skin under the light ofWOOD fluorescent lamp. Heavily colonizedfollicles become red-orange, characteristiclyfluorescent. Sebum has a pale yellowishfluorescence. Individuals who show invariablyintense fluoresce have a very large number of

20


de culoare roºu-oranj. Sebumul are o fluorescenþãuºor gãlbuie. Indivizii care prezintã fluorescenþãintensã prezintã invariabil un numãr foarte marede Propionilbacterium acnes iar pacienþii cuacnee vulgarã prezintã o fluorescenþã incom-parabil mai intensã [18] decât cei fãrã acnee.Fluorescenþa diminueazã semnificativ în urmatratamentelor cu antibiotice ºi anteseboreice.

În concluzie este necesarã scãderea secreþieide sebum, ce reprezintã suportul nutritiv pentruPropionilbacterium acnes (gel curãþare ºi geltratament conþinând atât extracte de plante–avocado: 5 alfa-avocuta, cu rol inhibitor asupra5 alfa-reductazei, alãturi de acid salicilic, acidglicolic ºi Zinc, cu rol bactericid) ºi tratarea cuantibiotic (metronidazol cu rol antiparazitar sibactericid) pentru eliminarea anaerobuluiPropionilbacterium acnes ºi sporirea eficacitãþiitratamentului topic.

Pacienþi ºi metode

Studiu a fost unicentric, randomizat, de tipsimplu orb, realizat pe o perioadã de 12sãptãmâni ºi a inclus 30 de voluntari caucazieni.Fiecare pacient a fost evaluat prin examen clinic,biochimic, hematologic, examen bacteriologic ºimicologic din pustule. Pentru clasificarea clinicãs-a utilizat scara Burton (23, 24) (Tabel 1).

Au fost recrutaþi pacienþii care nu aveauantecedente medicale recente (sub 30 zile),chirurgicale, anestezice sau de orice naturã sãafecteze zonele tegumentare sau structurile

Propionilbacterium acnes on the skin andpatients with acne vulgaris present anincomparably more intense fluorescence [18]than those without acne. Fluorescence diminishessignificantly after treatment with antibiotics andanteseborrheics.

As a conclusion, it is necessary to decreasethe secretion of sebum, considered to be thenutritional support for Propionilbacterium acnes(unsing cleansing gel and treatment gelcontaining the plant extract (avocado) 5 alpha-avocuta, ( a 5 alpha-reductase inhibitor), salicylicacid, glycolic acid and Zinc, for the bactericidalrole) and treatment with antibiotics (metro-nidazole with antiparasitic and bactericidal role)to eliminate anaerobic Propionilbacterium acnesand increasing efficacy of topical product.

Patients and methods

The trial was designed as unicentric,randomized, single blind, conducted over aperiod of 12 weeks and included 30 Caucasianvolunteers. Each patient was evaluated byclinical examination, biochemical, haemato-logical, bacteriological and mycological exa-mination of pustules. Burton classification scalewas used for clinical staging [23, 24] (Table I).

Patients who were recruited had no or recent(less than 30 days) medical or surgical history,anesthesy of any areas or underlying structuresaffecting the skin needed to be studied, and met

Grad 0 fãrã leziuni

Grad 1 comedoane închise, deschise ºi foarte puþine papule ºi pustule

Grad 2 comedoane închise, deschise mai multe papule ºi pustule, distribuite pe o suprafaþã mai mare

Grad 3 comedoane închise, deschise ºi multe pustule pe mai mult din jumãtate din faþã

Grad 4 comedoane închise, deschise ºi numãr mare de papule ºi pustule, chiar nodulare

Grad 5 toatã faþa prezintã comedoane închise, deschise, papule, pustule numeroase ºi noduli rari

Grad 6 toatã faþa prezintã comedoane închise, deschise, papule, pustule numeroase, numeroºi noduli, chiar dispuºi în placarde

Tabel 1. Clasificarea severitãþii acneei conform scalei Burton

Stage 0 no lesions

Stage 1 closed comedones, open comedones and few pustules

Stage 2 closed comedones, open comedones and more pustules, affecting a large area

Stage 3 closed comedones, open comedones and large number of papules and pustules, affecting 50% of the face area

Stage 4 closed comedones, open comedones and large number of papules and pustules, even nodular

Stage 5 all face presents closed comedones, open come-dones, many papules, pustules and rare nodules

Stage 6 all face presents closed comedones, open comedones, many papules, pustules numerous, nodules, even developed to placards

Table I. Burton clasification score for clinical staging

21


subiacente acestora necesare a fi studiate, ºi careîndeplineau urmatoarele criterii de includere: sex masculin/feminin; vârsta peste 18 ani;diagnosticaþi cu stadii uºoare ºi medii de acneevulgarã; având consimþãmântul liber exprimat,semnat în clar ºi indescifrabil dupã informareascrisã ºi verbalã a acestora asupra scopuluistudiului precum ºi a modalitãþii acestuia dedesfãºurare dar ºi asupra drepturilor acestora;excluºi din alte studii în desfãºurare.

S-au exclus persoanele care: sunt însãrcinate/alãpteazã, prezintã orice altã dermatozã/maladie acutã sau cronicã suprapusã diagnosti-cului primar de includere în studiu, care ar puteainterfera tratamentului sau l-ar putea afecta însensul apariþiei efectelor adverse sau nedorite,precum ºi subiecþi având un tratament înderulare, topic sau sistemic sau chiar întreruptdacã acesta a fost efectuat la mai puþin de 4sãptãmâni de la data începerii studiului.

Pacienþii prezentau o acnee uºoarã sau medie(gradul 1-2 ºi 3-4) (Figura 2), cu fototipuri alepielii variind de la tipul II la IV, caucazieni, ºi aufost împãrþiþi în douã grupe tratate diferit.Secvenþa de alocare a fost generatã folosindRandom Allocation Software v1.0.0. Tuturorpacienþilor li s-a fãcut o evaluare comparativã adouã zone simetrice (cei doi obraji). Întrucâtpacienþii din grup nu prezintã leziuni severenodulare (stadiile 5-6), macrofotografia folositãde noi în studiu (faþã/profil dreapta/stânga)reflectã corect tipul ºi gradul leziunilor de acnee(pentru cã trebuie þinut cont de faptul cãfotografic leziunile nodulare apar sub forma unorpapule). (Table 2)

the following inclusion criteria: male / female,age over 18 years old, diagnosed with early ormedium stages of acne vulgaris, having theirexpressed consent, signed and clearly writtenafter informing them about the purpose of thestudy and its development and also about theirrights, and who were excluded from otherstudies in progress.

They excluded subjects who: were pregnant /breastfeeding, had any other acute / chronicdermatosis or other condition superimposed onprimary diagnosis, which could interfere withtreatment or could affect the occurrence ofadverse or undesirable effects, and subjects withany ongoing treatment, topical or systemic, evendiscontinued if it was conducted less than 4weeks before the study began.

Patients had mild or moderate acne (grade 1-2 and 3-4), with skin phototypes ranging fromtype II to IV, Caucasians, and were divided intotwo groups differently treated. Allocationsequence was generated using the RandomAllocation Software v1.0.0. A comparativeassessment of two symmetrical parts (bothcheeks) was performed on all patients. Sincepatients did not have severe nodular lesions(stages 5-6), we used macrophotography (front /profile right or left) to accurately reflect the typeand degree of acne lesions (we must be kept inmind that nodular lesions appear as papules inphotography) (Table 2).

Secondary evaluation criteria were: clinicalquotation (injury severity) scale assessed using

Tabel 2. Criteriul principal de analizã (evaluare) folosit a fostreprezentat de scorul clinic al eficacitãþii globale evaluat decãtre investigator în cadrul vizitelor din vizita initialã ºisãptãmâna 4, 8, 12, dupã o scarã de la 1 la 6:

Neschimbat 0

Efect slab, difuz 1

Efect slab, dar omogen 2

Efect moderat, difuz 3

Efect moderat, dar omogen 4

Efect cvasitotal, dar care nu intereseazã întreaga zona atinsã 5

Efect total 6

Table 2. The primary analysis (evaluation) score used was theclinical global efficacy assessed by the investigator duringthe initial visit and the visits after 4, 8, 12 weeks using a 6stage scale

Unchanged 0

Weak diffuse effect 1

Thin, but uniform effect 2

Moderate, diffuse effect 3

Moderate, but homogeneous effect 4

Almost total effect, but not interesting the whole affected area 5

Total effect 6

22


Criterii secundare de evaluare au fost : cotaþiaclinicã (severitatea leziunilor) evaluatã dupã scaraBurton, precum ºi scorul de toleranþã a produselortestate. Folosirea macrofotografiei ca metodãstandardizatã cu ocazia fiecãrei vizite a permisurmãrirea evoluþiei în timp a leziunilor. (Tabel 3)

Suplimentar s-a realizat o autoevaluare afiecãrui pacient folosind un chestionar ce includeo evaluare a scorului clinic similarã celei realizatede cãtre investigator, precum ºi un set de 8întrebãri prin care sunt apreciate calitãþilecosmetice ale fiecãrui produs primit.

Formulele concepute pentru topice conferã oabsorbþie maximã a produselor testate. Acestea aufost supuse testãrilor reglementate prin nor-mativele Consiliului European cu privire la tole-rabilitatea cutanatã ºi ocularã, a proprietãþilorhidratante cât ºi a potenþialului sensibilizant.Aplicaþiile cutanate locale s-au fãcut de 2 ori pe zi.

Nu au fost permise alte asocieri de tratamenteîn afara celor stabilite.

15 pacienþi au fost trataþi pe un obraz cu gelulde curãþare (acid salicilic 1%, zinc 0.5% ) + gelultratament seboregulator antibacterian (acidglicolic 6%, zinc 1%, 5 alfa avocuta 1% ), iar pecelãlalt obraz cu o cremã neutrã având aceleaºicaracteristici din punct de vedere al texturii ºiculorii. Ceilalþi 15 pacienþi au fost trataþi cu gelulde curãþare + gelul tratament seboregulatorantibacterian la care s-a adãugat metronidazol0,75%, iar pe celãlalt obraz cu aceeaºi cremãneutrã ca ºi la primul grup.

Analizã statisticã

Toate analizele statistice au fost procesatefolosind programul SPSS 19.0 for Windows.Pentru toate testele, o valoare p<0.05 a fostconsideratã ca fiind semnificativã statistic.

Burton scale and tolerance score. Using macro-photography as standardized method on eachvisit allowed the evaluation of the temporalevolution of lesions (Table 3).

In addition to that, a self-assessment made ofeach patient using a questionnaire was also

performed, including an assessment of clinicalscore similar to that made by the investigator,and a set of eight questions evaluating cosmeticqualities of each product received.

Topical formulations are designed to givemaximum absorption of the tested products.They were subjected to testing standardsregulated by the European Council on skin andocular tolerability, moisturizing properties andsensitizing potential. Local skin applicationswere made 2 times a day.

No other associated treatments werepermitted, except for the ones mentioned in thetrial protocol.

15 patients were treated with cleansing gel(1% salicylic acid, zinc 0.5%) + gel seboregulatorantibacterial treatment (glycolic acid 6%, zinc 1%,5 alpha lawyer 1%) on half face (cheek) and onthe other cheek a neutral cream with the samecharacteristics in terms of texture and color wasused for comparison. The other 15 patients weretreated with cleansing gel + seboregulator gelplus, antibacterial therapy (0.75% metronidazole)on half face compared to the same neutral creamas the first group, on the other half of the face.

Statistical analysis

All statistical analyses were performed usingSPSS 19.0 software for Windows. For all tests avalue of p<0.05 was considered as statisticallysignificant.

Tabel 3. Toleranþa a fost cotatã pe o scarã de la 0 la 4

Absenþa oricãrui efect advers 0

Efect advers nesemnificativ 1

Efect advers moderat 2

Efect advers important-necesitã întrerupere 3temporarã a administrãrii produselor test

Efect advers sever-necesitã încheierea prematurã 4a studiului ºi tratament de specialitate al patologiei nou apãrute

Table 3. Tolerance was rated on a scale of 0-4

Absence of any adverse effect 0

Insignificant adverse effect 1

Moderate adverse effects 2

Important side effect, requiring temporary 3interruption of the administration of test product,

Severe adverse effect, requiring premature ending 4of the study and specialty treatment of emerging pathology).

23


Rezultate

Dintre cei 15 pacienþi trataþi cu asocierea deseboregulator ºi Metronidazol, în urma evaluãriifãcute de cãtre investigator, rezultã:

• 12 pacienþi (80%) au înregistrat un efecttotal cu dispariþia simptomelor dupã 4sãptãmâni.

• 3 pacienþi (20%) au obþinut remisie totalãdupã 8 sãptãmâni (un pacient a prezentatdupã 4 sãptãmâni un efect cvasitotal, iar 2dintre ei un efect moderat omogen).

Dintre cei 15 pacienþi trataþi cu seboregulatorfãrã asociere de Metronidazol, în urma evaluãriirezultã:

• 2 pacienþi (13,3%) au prezentat remisietotalã dupã 4 sãptãmâni de tratament.

• 3 pacienþi (20%) au prezentat remisiecvasitotalã dupã 4 sãptãmâni de tratament,iar efect total dupã 8 sãptãmâni.

• 5 pacienþi (33,3%) au obþinut dupã 4sãptãmâni de tratament un efect slab daromogen, dupã 8 sãptãmâni remisiemoderatã, dar omogenã, iar dupã 12sãptãmâni efect total.

Restul de 5 pacienþi (33,3%) nu au obþinutefectul total dupã 12 sãptãmâni, dar au preferatsã rãmânã sub tratament ºi sub observaþie, astfel:

• 4 subiecþi (26,6%), dupã 4 sãptãmâni detratament au prezentat un efect slab difuz,dupã 8 sãptãmâni de tratament efectmoderat omogen, dupã 12 sãptãmâni efectcvasitotal, iar dupã 16 sãptãmâni efecttotal.

• 1 subiect (6,6 %) a avut dupã 4 sãptãmânide tratament efect slab difuz, dupã 8sãptãmâni efect slab dar omogen, dupã 12sãptãmâni efect moderat omogen, dupã 16sãptãmâni efect cvasitotal, dupã 20sãptãmâni efect total (Figura 1).

Din punct de vedere al toleranþei, 3 pacienþi(10% din totalul de participanþi) au înregistratefecte secundare neînsemnate la preparatele cuacid salicilic pe zona pe care s-a aplicat cremaactivã comparativ cu cealaltã zonã pe care s-aaplicat crema neutrã, ce nu a prezentat reacþiiadverse, efecte care au cedat spontan, ºi care auscazut în intensitate, dispãrând pe parcursultratamentului, ce nu a necesitat întrerupere.

Restul pacienþilor nu au înregistrat efectesecundare de nici un fel.

Results

Of the 15 patients treated with the combi-nation of seboregulator and metronidazole, theevaluation made by the investigator resulted asfollows:

• 12 patients (80%) had a total effect: thedisappearance of symptoms after 4 weeks.

• 3 patients (20%) achieved complete remis-sion after 8 weeks (one patient had almosttotal effect after 4 weeks and 2 of them hadan homogeneous, moderate effect).

Of the 15 patients treated with e sebo-regulator without association of metronidazole,the evaluation resulted as follows:

• 2 patients (13.3%) had complete remissionafter 4 weeks of treatment.

• 3 patients (20%) experienced almostcomplete remission after 4 weeks oftreatment and total effect after 8 weeks.

• 5 patients (33.3%) obtained a weak buthomogeneous effect after 4 weeks oftreatment, medium but homogeneousremission after 8 weeks , and total effectafter 12 weeks.

The remaining 5 patients (33.3%) did notobtain the total effect after 12 weeks but preferredto remain under treatment and observation, asfollows:

• 4 subjects (26.6%) showed a weak, diffuseeffect after 4 weeks of treatment, a mode-rate homogeneous effect after 8 weeks,almost total effect after 12 weeks andcomplete effect after 16 weeks of treatment.

• 1 subject (6.6%) had a diffuse effect after 4weeks of treatment, weak but uniformeffect after 8 weeks, homogeneous,moderate effect after 12 weeks, after 16weeks almost total effect, total effect after20 weeks. (Figure 1) .

In terms of tolerance, 3 patients (10% ofparticipants) reported minor side effects forpreparations with salicylic acid in the activecream that was applied compared to the otherarea the neutral cream has been applied on,which did not show adverse effects. These sideeffects dissapeared spontaneously, and decreasedin intensity and disappear during treatment,which did not require interruption. Theremaining patients have not experienced any sideeffects.

24


Discuþii

Prezenþa în grupul de studiu ºi a persoanelormature, nu doar a tinerilor, dovedeºte faptul cãacneea, deºi boalã a adolescenþei, netratatã sautratatã inconsecvent îºi poate prelungi evoluþia ºispre maturitate. Toþi pacienþii incluºi au prezentatleziuni de acnee încã din adolescenþã. Dintre cei30 de subiecþi, 70% au vârste cuprinse între 18 ºi30 de ani (din 21 de subiecþi, 11 au între 18 ºi 20ani), iar 30% se situeazã între 30 ºi 55 ani (Figura7). Deºi toþi pacienþii au prezentat acnee dinadolescenþã, 46,6% nu au efectuat niciuntratament, 26,6% au fãcut un singur tratament,16,6% douã tratamente anterioare, iar 10% 3tratamente anterioare (Figura 6). Menþionãm cãaceste tratamente anterioare au fost efectuate cucel puþin o lunã înaintea începerii studiului.Prezenþa mai numeroasã a pacientelor de sexfeminin (66%) faþã de sexul masculin (34%), sedatoreazã probabil faptului cã acestea sunt multmai preocupate de aspectul fizic decât bãrbaþii(Figura 8). Uneori prezentarea la medic ºideterminarea pacientului de a duce la capãt untratament s-au datorat schimbãrii locului demuncã (bancã, relaþii cu publicul), care nupermitea prezenþa leziunilor de acnee pe faþã.Alte douã paciente au ajuns la dermatologindirect, trimise de ginecologul care le tratapentru infertilitate ºi respectiv menstre ne-regulate, amândouã pacientele prezentând ovarepolichistice ºi discret hirsutism.

Ca o observaþie, prezentarea la doctor s-afãcut în momentul în care pacientul a avut omotivaþie solidã ºi a conºtientizat aspectele legatede implicaþiile psihosociale ale afecþiunii, întrucâtacneea rãmâne o afecþiune cutanatã cu un impactvizual deosebit, boala apãrând îndeosebi lanivelul feþei.

Dupã mediul de viaþã, 73% dintre pacienþiproveneau din mediul urban ºi 27% din mediulrural. (Figura 4)

Deºi studiul trebuia derulat pe parcursul a 12sãptãmâni, totuºi din curiozitate am prelungittratamentul (ca interval de timp) pentru cei careîn momentul împlinirii celor 12 sãptãmâni detratament prezentau o ameliorare importantã,dar nu o remisie. S-a dovedit cã acestora le-aumai fost necesare încã 4 ºi respectiv 8 sãptãmânide tratament pentru a înregistra dispariþia

Discussion

Presence in the study group of maturesubjects, not just young subjects, shows that acne,although disease of the adolescence, untreated orinconsistently treated could extend it’sdevelopment to adulthood. All patients had acnelesions of since adolescence. Of the 30 subjects,70% are between 18 and 30 years old (out of 21subjects, 11 were between 18 and 20 years old)and 30% are between 30 and 55 years old.Although all patients had acne in adolescence,46.6% did not carry out any treatment, 26.6% hadone treatment, 16.6% two prior therapies and 10%three prior therapies. Note that these previoustreatments were performed at least one monthbefore the study began. Larger presence of femalesubjects (66%), more than males (34%), isprobably due to the fact that they are moreconcerned of their look than men. Sometimes thevisit to the doctor and patient’s determination tocarry through the treatment were due to jobchanges (bank, public relations), which did notallow the presence of acne lesions on the face.Two other patients reached indirectly thedermatologist, first going to gynecologist forinfertility and irregular periods, polycysticovaries, both patients presenting discretehirsutism.

As an observation, visit to the doctor wasperformed when the patient had a strongmotivation and realized the psychosocialimplications of this condition, skin disorders asacne remaining a particular condition with astrong visual impact, occurring especially in theface.

Judging by the living environment, 73% ofpatients were from urban areas and 27% in ruralareas.

Although the study was planned for a periodof 12 weeks, however out of curiosity I extendedtreatment period for those who on reaching the12 weeks period showed significant improve-ment but not remission. It turned out that thisextension of period has been been proved to beeffective for 4 to 8 weeks of treatment dependingon the stage to record the disappearance of

25


simptomelor. Aproximativ 50% dintre subiecþiaveau acnee atât pe faþã cât ºi pe toraceleposterior, umeri, braþe mai frecvent. Tratamentuls-a derulat concomitent cu cel pentru faþã cuaceleaºi rezultate. Precizãm de asemenea, cãvizitele tuturor acestor pacienþi din studiu, nu s-au terminat odatã cu închiderea acestuia. Ei aucontinuat sã se prezinte la consultaþii, fie pentrudepigmentãri, fie pentru umplerea cu acidhialuronic a cicatricilor atrofice, fie pentru pro-cedee de microdermabraziune sau peelingchimic, cu scopul eliminãrii hiperpigmentãrilorreziduale, sau a cicatricilor atrofice, ca de altfel ºipentru continuarea tratamentelor trofice sebo-regulatoare, de întreþinere.

În cadrul investigaþiilor s-au fãcut deter-minãri biochimice, hematologice, markeriinfecþioºi, examene parazitologice, determinãrihormonale, etc.

Ca urmare: • La examenul bacteriologic, din pustule s-

au evidenþiat germeni Gram negativi(Escherichia coli, Enterobacter aerogenes,Klebsiella pneumoniae, etc), frecvent la ceicare au fãcut anterior tratamente cuantibiotice orale, sau coci (Staphilococcusepidermitis).

• A fost evidenþiatã ºi prezenþa Propionil-bacterium acnes (Gram pozitiv, Micro-aerofil, care creºte cel mai bine în condiþiistrict anaerobe, deci intraforicular), lamajoritatea pacienþilor. Evidenþierea s-afãcut cu lampa WOOD pe culturi prinvizualizarea porfirinelor produse dePropionil bacterium acnes.

• În 8 cazuri s-a observat prezenþa Pityro-sporum la nivelul foliculului pilosebaceu.

• La determinãrile biochimice o persoanã aprezentat ASLO = 600 u/ml ºi un exudatfaringian cu Streptococ Beta Hemoliticprezent (pacienta fiind profesoarã de înot,având 31 ani, petrecând în piscinãaproximativ 8 ore pe zi ºi având unîndelungat contact cu clorul atât în aerulumed dar ºi în apã, cãldura umedã deter-minând o hidratare ductalã exageratã,favorizând leziunile de acnee), iar o alta aprezentat un PCR = 3,95 mg/l chimieumedã (biochimie); hematologic avea:

symptoms. Approximately 50% of subjects hadacne on both front and back torso, shoulders andarms more frequently. Treatment was carried outsimultaneously as for the face with the sameresults. It is important to note also that all thesepatients did not end visits after study closure.They continued to visit the dermatologist, foreither depigmentation or hyaluronic acid fillingof atrophic scars, or microdermabrasion orchemical peel procedures in order to eliminateresidual hyperpigmentation or atrophic scars, as well as for further seboregulator trophictreatment and maintenance.

The investigations included biochemical,haematological, infectious markers, parasito-logical examinations, hormonal determinations,etc.

As a result:• The bacteriological examination of

pustules revealed the presence of Gramnegative bacteria (Escherichia coli, Entero-bacter aerogenes, Klebsiella pneumoniae,etc.) or cocci (Staphylococcus epidermidis),often in those patients who have receivedprevious treatment with oral antibiotics.

• The presence of Propionylbacterium acneswas highlighted (Gram positive, micro-aerophilic, which grows best under strictlyanaerobic, specifically intraforicular) inmost patients. Highlighting was made byviewing the porphyrins produced byPropionylbacterium acnes culture usingthe WOOD lamp.

• The presence of Pityrosporum insidepilosebaceous follicle was observed in 8cases.

• One patient presented biochemical deter-mination of ASLO = 600 u / ml and betahemolytic streptococcal positive pha-ryngeal exudate (the patient was aswimming teacher, 31 years old, spendingabout 8 hours a day in the pool and havinglong contact with the chlorine in moist airand in water, moist heat causing excessiveductal hydration, promoting acne lesions),and another patient presented a PCR = 3.95

26


WBC = 15,10*103/mm3, cu Ne =9,54*103/mm3, Eo= 0,548*103/mm3, Mo =1,050*103/mm3; la coagulare fibrinogenula fost 450 mg/dl, iar ca markeri infecþioºiprezenta anticorpi antihelicobacter pylori= 7,02 U/ml (singura pacientã cu acneevulgarã care a prezentat helicobacterpylori). Aceastã pacientã a fostdiagnosticatã histopatologic cu dermatitãpustuloasã infundibularã ºi folicularã (s-afãcut chiar recomandarea unui diagnosticdiferenþial între o dermatitã pustuloasãinfundibularã ºi folicularã infecþioasã -bacterianã, fungicã sau viralã, ºi odermatitã pustuloasã infundibularã ºifolicularã fãrã agent infecþios). Pesecþiunile colorate H&E nu s-au identificatagenþi infecþioºi sau modificãri citopaticevirale, dar s-a recomandat efectuarea unorculturi prin leziunile pustuloase, care auarãtat prezenþa Staphilococus aureushemoliticus pentru care a efectuat ºitratament conform antibiogramei. Aceastãpacientã în vârstã de 37 ani a fostinvestigatã aproximativ 2 ani pentru LEC,Paraporiazis acut, Papulozã Limfomatoidãºi Papulozã atroficã DEGOS, derulând oserie de tratamente cum ar fi Dapsonã,Prednison, antibiotice orale, etc., darnimeni nu a tratat-o de acnee, pacientaprezenta foarte multe leziuni rezidualecicatriciale, unele hiperpigmentate, dar ºileziuni active papulopustuloase. Sur-prinzãtor rãspunsul la tratamentul topic afost foarte rapid (4 sãptãmâni). În afaratratamentelor generale nimeni niciodatãnu i-a recomandat vreun topic în afarabetadinei soluþie. Precizãm cã restulpacienþilor nu au prezentat modificãribiochimice sau hematologice.

• Din punct de vedere endocrinologic: s-aconstatat cã toate femeile prezentau oexacerbare premenstrualã a acneei. Nu s-aputut dovedi cã ar exista o variaþie asecreþiei de sebum sau a compoziþieiacestuia pe parcursul ciclului menstrual.Cele trei paciente cu acnee postmenopauzã (care aveau istoric de acnee)au prezentat la analize discret hiper-

mg / l wet chemistry (biochemistry),hematology: WBC = 15.10 * 103/mm3, withWe = 9.54 * 103/mm3, Eo = 0.548*103/mm3, Mo = 1.050 * 103/mm3;fibrinogen was recording a value of 450 mg/ dl, and infectious markers antihelico-bacter pylori antibodies = 7.02 U / ml (onepatient who presented helicobacter pyloriassociated to acne vulgaris). This patientwas histologically diagnosed with pustularinfundibular and follicular dermatitis(there was even recommended adifferential diagnosis between pustularinfundibular dermatitis with follicularinfections - bacterial, fungal or viral, andpustular infundibular and folliculardermatitis non-infectious agent. In sectionsstained H & E infectious agents were notidentified nor viral cytopathic changes, butrecommendation for performing culturesthrough pustular lesions was made, latershowing the presence Staphilococushemoliticus aureus which indicated theadequate treatment according toantibiogram. This 37 years old patient wasinvestigated for about two years forChronic Lupus, Acute Parapsoriasis,Atrophic Lymphomatoid Papulosis andDEGOS Papulosis, scrolling for a series oftreatments such as dapsone, prednisone,oral antibiotics, etc., but no one treated heracne, this patient having many residualinjuries, some hyperpigmented, and activepapulopustulosa lesions.

• Surprisingly response to topical therapywas very rapid (4 weeks). Besides neveradvised general treatments, only Betadinesolution was reccomended. The remainingpatients showed no biochemical orhematological changes.

• From the endocrinologist’s point of view: itwas found that all women hadpremenstrual exacerbation of acne, unableto prove that there was a variation ofsebum secretion and its compositionduring the menstrual cycle. The three

27


androgenism (fãrã a prezenta hirsutism).Dintre celelalte paciente doar douãprezentau hiperantrogenism: cea de 18 anifãcuse în acest sens tratament cu Siofortimp de 2 ani (ºi pentru reglarea ciclurilormenstruale), iar cealaltã pacientã de 19 ania fost tratatã de endocrinolog cuspironolactonã. Ambele au avut o încer-care anterioarã de tratare a acneei. În restexamenele endocrinologice nu au pre-zentat modificãri. O singurã pacientã învârstã de 36 de ani, care prezenta acneeuºoarã gradul 2 ºi hirsutism, s-a constatatcã prezenta ºi ovare polichistice, asociatecu sterilitate, deci un posibil sindrom PCO,pentru care efectua tratament endocrino-logic adecvat.

• Din punct de vedere al dietei, singuraobservaþie fãcutã de cãtre 4 dintre pacienþia fost cã de fiecare datã (în mod repetat) înurma consumului exagerat de ciocolatã auînregistrat un numãr crescut de leziunipapulopustuloase.

Evoluþie

Cei 15 pacienþi trataþi doar cu keratolitic,seboregulator antibacterian, antiinflamator, fãrãmetronidazol au avut o evoluþie mai lentã,necesitând un interval mai mare de timp catratament (peste 8 sãptãmâni), în vedereaobþinerii unei remisii (Figura 3).

Menþionãm un lucru foarte important ºianume faptul cã am ales formele uºoare ºimoderate de acnee (Figura 5) pentru a puteaobþine dispariþia leziunilor, nu doar ameliorãri(folosind aceste tratamente topice: antiinflamator,antibacterian, seboregulator, keratolitic), întrucâtscopul a fost sã nu apelãm la alte scheme maicomplexe de tratament care ar fi fost necesarepentru o formã mai severã de acnee.

Precizãm cã pacienþii care au fãcut anteriorstudiului diferite tratamente endocrinologice(pentru reglarea menstrelor, pentru hiper-androgenism, dismenoree) sau cu antibioticeorale (la cei cu exudate faringiene, nazale, etc cuprobleme în sfera ORL), sau alte tratamenteantiacneice, au intrat în studiul nostru dupã celpuþin o lunã de pauzã.

patients with acne after menopause (whohad a history of acne in the past) reporteddiscrete hiperandrogenism (withouthirsutism). Of the other patients, only twohad hiperantrogenism: one 18 years oldfemale who had SIOFOR for 2 years astreatment (to regulate menstrual cycles),and one 19 years old female previouslytreated by endocrinologist with spirono-lactone. Both had a previous attempt foracne treatment. Otherwise endocrino-logical examinations showed no changes.One female, 36 years old, which showedmild acne and hirsutism stage 2, wasfound to present polycystic ovariesassociated with sterility, considering apossible PCO syndrome, for whichappropriate endocrinological treatmentwas reccomended.

• In terms of diet, the only remark made byfour of the patients was that every time(repeatedly) from excessive consumptionof chocolate a high number ofpapulopustulosa lesions were reported.

Evolution

The 15 patients treated with keratolytic,seboregulator antibacterial, anti-inflammatorywithout metronidazole had a slower rate ofremission, requiring a longer period of time astreatment (more than 8 weeks) to achievecomplete results.

It is important to mention the fact that wehave chosen mild and moderate forms of acne inorder to obtain complete disappearance oflesions, not only improvements (using thesetopical treatments: anti-inflammatory, anti-bacterial, seboregulator, keratolytic), since thegoal was to not seek other more complextreatment regimens that would have beennecessary for a more severe form of acne.

The patients who have received previousendocrine treatments (to regulate menses, forhiperandrogenism, dysmenorrhea) or oralantibiotics (those with pharyngeal exudates,

28


Procentual, dintre cei 15 pacienþi trataþi fãrãMetronidazol, 67% au rãspuns dupã 12sãptãmâni sau mai mult de tratament, 20% dupã8 sãptãmâni de tratament ºi doar 13% dupãnumai 4 sãptãmâni de tratament, spre deosebirede ceilalþi trataþi ºi cu Metronidazol care au avutnevoie de 4 sãptãmâni de tratament pentru 80%dintre ei, ºi de 8 sãptãmâni de tratament pentru20% dintre ei. Dintre cei 15 pacienþi trataþi fãrãMetronidazol:

• 2 pacienþi (13,3%) au înregistrat remisie în4 sãptãmâni de tratament;

• 3 pacienþi (20%) au înregistrat remisie în 8sãptãmâni de tratament;

• 5 pacienþi(33,3%) au înregistrat remisie în12 sãptãmâni de tratament;

• 4 pacienþi (26,6%) au înregistrat remisie în16 sãptãmâni de tratament;

• 1 pacient (6,6 %) a înregistrat remisie în 20de sãptãmâni de tratament.

Dintre cei 15 pacienþi trataþi ºi cu Metro-nidazol:

• 2 pacienþi (80%) au avut nevoie de 4sãptãmâni de tratament;

• 3 pacienþi (20%) au avut nevoie de 8sãptamâni de tratament.

Concluzii

Aºa cum se poate observa din acest studiu, oparte dintre pacienþi au mai încercat anteriordiferite terapii (cu rezultate satisfãcãtoare), dargreºeala tuturor a fost una singurã ºi anume:dupã obþinerea unor ameliorãri importante sauchiar a unei remisii, pacienþii au oprit tratamentulsau au apelat la diferite creme cosmetice deîntreþinere, care nu se adresau tipului lor de tenmixt - seboreic, aceastã conduitã fiind biletulsigur cãtre recidivã. De aceea ei trebuiescinformaþi de la început cã dupã dispariþialeziunilor, tratamentul se simplificã gradat dar nuse opreºte pentru a obþine un succes de lungãduratã.

Din studiu reiese clar faptul cã un tratamenttopic mai complex cu o asociere de antibiotic -Metronidazol duce la rezultate mult mai rapide,în acest fel pacientul devenind mult mai optimist,mai încrezãtor ºi mai rãbdãtor în a duce totul labun sfârºit.

nasal, etc. in the field of ENT problems), or otheracne treatments have been included in our trialafter at least one month break.

Out of the 15 patients treated withoutmetronidazole, 67% responded after 12 weeks ormore of treatment, 20% after 8 weeks of treatmentand only 13% after only 4 weeks of treatment,unlike the others treated with metronidazole. Ittook 4 weeks for 80% of them, and 8 weeks for20% of them to reach complete results.

Of the 15 patients treated without metro-nidazole:

• 2 patients (13.3%) had remission within 4weeks of treatment;

• 3 patients (20%) had remission within 8weeks of treatment;

• 5 patients (33.3%) showed remission in 12weeks;

• 4 patients (26.6%) had remission within 16weeks of treatment;

• 1 patient (6.6%) showed remission in 20weeks.

Of the 15 patients receiving metronidazole:• 12 patients (80%) needed treatment for 4

weeks;• 3 patients (20%) needed treatment for 8

weeks.

Conclusions

Some patients have previously tried varioustherapies (with satisfactory results), but themistake was only one, as follows: after obtainingsignificant improvement or even remission,patients stopped treatment or have resorted tovarious cosmetic creams maintenance notaddressed to their skin type mixed- seborrheic,this certainly leading to relapse. Therefore theymust be informed at the outset that after thedisappearance of lesions, treatment is easily butgradually stopped to get a long-term satisfactoryresult.

It is clear that a more complex topicaltreatment with a combination of antibiotics -metronidazole leads to results much faster, thusmaking the patient more optimistic and moreconfident to carry it all to the end.

29


Figura 1. Remisia în timp a leziunilor pe cele douã grupuri de pacienþi (în paralel)Figure 1.Evolution in time for the two groups

Figura 2. Repartizarea celor 30 de pacienþi, în funcþie de tipul ºigradul de severitate al acneei:Severitatea acneei a fost cuantificatã în 7 trepte distinctenotate de la 0 la 6:0 = fãrã leziuni1 - 2 = leziuni uºoare3 - 4 = leziuni moderate5 - 6 = leziuni severe

Figure 2 Distribution of the patients included in the trial,depending on type and severity score:Acne severity was quantified in 7 distinct stagesmarked from 0 to 6:0 = no damage1-2 = mild lesions3-4 = moderate damage5-6 = severe damage

30


Figura 3. Repartizarea graficã a celor 30 de pacienþi, careprezintã remisia completã a leziunilor, în funcþie de timp(lotul celor 15 pacienþi trataþi cu o singurã cremã ºi lotulcelorlalþi 15 trataþi cu douã creme):

• La vizita 1 (4 sãptãmâni), leziunile au dispãrutcomplet la 2 pacienþi




• La vizita 5 (20 sãptãmâni), leziunile au dispãrutcomplet la 1 pacient

Figure 3. Graphical distribution of the 30 patients showingcomplete resolution of lesions, depending on the time (groupof 15 patients treated with one cream and other 15 treatedgroup with two creams)

• At visit 1 (4 weeks), the lesions completelydisappeared on 2 patients




• At visit 5 (20 weeks), the lesions completelydisappeared on 1 patient

31


A: Dispariþia completã a leziunilor în grupul celor 15 pacienþi trataþi cuo singurã cremã se prezintã astfel:

• Dispariþia simptomelor în 1-2 vizite (4-8 sãptãmâni) la 26,7%din pacienþi

• Dispariþia simptomelor în 3-5 vizite (12-20 sãptãmâni) la 73,3%din pacienþi

A: complete disappearance of lesions in the group of15 patients treated with single cream is asfollows:

• symptoms disappear within 1-2 visits (4-8weeks) to 26.7% of patients

• symptoms disappear within 3-5 visits (12-20 weeks) to 73.3% of patients

B: Dispariþia completã a leziunilor în grupul celor 15 pacienþi trataþicombinat cu cele douã creme:

• Dispariþia simptomelor la prima vizitã (4 sãptãmâni) la 80%din pacienþi

• Dispariþia simptomelor la a doua vizitã (8 sãptãmâni) la 20%din pacienþi

B: Complete disappearance of lesions in the group of15 patients treated in combination with twocreams:

• symptoms disappear at the first visit (4weeks) to 80% of patients

• symptoms disappear in the second visit (8weeks) to 20% of patients

32


Figura 4. Repartizarea celor 30 de pacienþi din studiu dupã mediul deviaþã• Mediu urban 73%• Mediu rural 27%

Figure 4. Distribution of the 30 patients in thestudy after living environment• 73% urban area• 27% rural area

Figura 5. Repartizarea pacienþilor dupã gradul de severitate al acneei(pacienþii din studiu, în mod aleator, s-au constituit în 2 grupe egale):• Acnee vulgarã uºoarã la 50% din pacienþi• Acnee vulgarã moderatã la 50% din pacienþi

Figure 5. Distribution of patients according toseverity of acne (patients in the study, wererandomly allocated in two equal groups):• mild acne vulgaris in 50% of patients• moderate acne vulgaris in 50% of patients

33


Figura 6. Repartizarea pacienþilor dupã numãrul tratamentelorefectuate anterior:• 1 tratament anterior 46%• 2 tratamente anterioare 27%• 3 tratamente anterioare 17%• 4 tratamente anterioare 10%

Figure 6. Distribution of patients by the number oftreatments previously performed:• one previous treatment 46%• two previous treatments 27%• three previous treatments 17%• four previous treatments 10%

Figura 7. Repartizarea celor 30 de pacienþi dupã vârstã

• 18-30 ani - 70% (din 21 de subiecþi, 11 au între 18 ºi 20 ani)

• 30-55 ani - 30%

Figure 7. Distribution of patients by age 30

• 18-30 years - 70% (from 21 subjects, 11 werebetween 18 and 20 years)

• 30-55 years - 30%

34


Cazul 1: Pacientã, 37 ani, a prezentat unPCR=3,95mg/l chimie umedã (biochimie);hematologic avea: WBC = 15,10*103/mm3, cu Ne= 9,54*103/mm3, Eo= 0,548*103/mm3, Mo =1,050*103/mm3; la coagulare fibrinogenul a fost450 mg/dl, iar ca markeri infecþioºi prezentaanticorpi antihelicobacter pylori = 7,02 U/ml(singura pacientã cu acnee vulgarã care aprezentat helicobacter pylori). Aceastã pacientã afost diagnosticatã histopatologic cu dermatitãpustuloasã infundibularã ºi folicularã. S-a fãcutchiar recomandarea unui diagnostic diferenþialîntre o dermatitã pustuloasã infundibularã ºifolicularã infecþioasã - bacterianã, fungicã sauviralã, ºi o dermatitã pustuloasã infundibularã ºifolicularã fãrã agent infecþios. Pe secþiunilecolorate H&E nu s-au identificat agenþi infecþioºisau modificãri citopatice virale, dar s-arecomandat efectuarea unor culturi din leziunilepustuloase, care au arãtat prezenþa Staphilococusaureus hemoliticus pentru care a efectuat ºitratament conform antibiogramei. Aceastãpacientã în vârstã de 37 ani a fost investigatãaproximativ 2 ani pentru LEC, Paraporiazis acut,Papulozã Limfomatoidã ºi Papulozã atroficãDEGOS, derulând o serie de tratamente cum ar fiDapsonã, Prednison, antibiotice orale, etc., darnimeni nu a tratat-o de acnee, pacienta prezentafoarte multe leziuni reziduale cicatriciale atrofice,unele hiperpigmentate, dar ºi leziuni activepapulopustuloase.

Case 1: Patient, 37 years, presented a PCR =3.95 mg / l wet chemistry (biochemistry),hematology: WBC = 15.10 * 103/mm3, with We =9.54 * 103/mm3, Eo = 0.548 *103/mm3, Mo = 1.050* 103/mm3; fibrinogen was recording a value of450 mg / dl, and infectious markers anti-heli-cobacter pylori antibodies = 7.02 U / ml (onepatient who presented helicobacter pyloriassociated to acne vulgaris). This patient washistologically diagnosed with pustular infundi-bular and follicular dermatitis (there was evenrecommended a differential diagnosis betweenpustular infundibular dermatitis with follicularinfections - bacterial, fungal or viral, and pustularinfundibular and follicular dermatitis non-infectious agent. In sections stained H & Einfectious agents were not identified nor viralcytopathic changes, but recommendation forperforming cultures through pustular lesionswas made, later showing the presence Staphilo-cocus hemoliticus aureus which indicated theadequate treatment according to antibiogram.This 37 years old patient was investigated forabout two years for Chronic Lupus, AcuteParapsoriasis, Atrophic Lymphomatoid Papu-losis and DEGOS Papulosis, scrolling for a seriesof treatments such as dapsone, prednisone, oralantibiotics, etc., but no one treated her acne, thispatient having many residual injuries, some

Figura 8. Repartizarea celor 30 de pacienþi dupã sex:

• Femei 66%

• Bãrbaþi 34%

Figure 8. Distribution of 30 patients by gender:

• Women 66%

• Men 34%

35


Surprinzãtor rãspunsul la tratamentul topic afost foarte rapid (4 sãptãmâni). În afaratratamentelor generale nimeni niciodatã nu i-arecomandat vreun topic în afara betadinei soluþie.Cu o lunã înainte de intrarea în studiu, i s-aefectuat tratamentul standard pentruhelicobacter pylori, ºi anume : 7 zile a primtOmeprazol 40 mg/zi, Azitrox 500 mg/zi,Amoxicilinã 1 g/zi, iar urmãtoarele 23 de zile aprimit Omeprazol 20 mg/zi, dupã care i s-aefectuat determinarea antigenului H. pylori dinmaterii fecale, care a fost negativ. La reevaluareaformulei leucocitare, la 7 zile dupã terminareatratamentului oral antistafilococic, precum ºi altratamentului antiH. Pylori, s-a constatatnormalizarea acestuia. Peste o lunã, la intrarea înstudiu, pacienta arãta, ca în imaginile urmãtoare,fiind încadratã la o formã de acnee moderatã,gradul 4, cu leziuni cicatriciale atrofice ºi leziunireziduale hiperpigmentate, atât pe faþã, decolteuºi membrele superioare. Pacienta a primittratament asociat gel de curãþare, gelseboregulator ºi metronidazol ºi uimitor a avutrãspuns favorabil dupã 4 sãptãmâni detratament. Precizãm situaþia particularã a acestuicaz, care constã în faptul cã la aproximativ 2sãptãmâni dupã întreruperea acestui tratamentlocal, leziunile cicatriciale se redeschid,transformându-se în leziuni intens eritematoase,aproape erozive, lipsite de exudaþie, iar leziunileacneice reapar treptat ºi au o evoluþie foarterapidã (aproximativ 24 de ore) în ceea ce priveºtetrecerea papulã-pustulã-crustã, ca ulterior sãrãmãnã o cicatrice atroficã, mai mult sau maipuþin evidentã sau o leziune rezidualãhiperpigmentatã. Pacienta aºa cum am arãtat maisus, a fost urmãritã ºi dupã ieºirea din studiu ºi s-a constatat cã în situaþia de recidivã,simptomatologia dispare la fel de rapid ca primadatã (4 sãptãmâni), aplicând local acelaºitratament asociat, ºi anume gelul de curãþare,gelul seboregulator ºi metronidazol. Încontinuare, profitând de dispariþia leziuniloracneice ºi închiderea leziunilor de tip eroziv,pacientei i s-a aplicat un tratament dedepigmentare cu cremã ( Neotone radiance), ºipeeling chimic. Toate tratamentele topice au fostaplicate atât pe faþã cât ºi pe corp, cu rezultatesimilare. Menþionãm cã pacienta a fost nu numaifoarte conºtincioasã, dar era ºi în cunoºtinþã decauzã, fiind medic de familie.

hyperpigmented, and active papulopustulosalesions.

Surprisingly response to topical therapy wasvery rapid (4 weeks). Besides never advisedgeneral treatments, only Betadine solution wasreccomended. One month before trial inclusonshe performed a standard treatment forHelicobacter pylori, namely: 7 days receivingOmeprazole 40 mg / day, Azitrox 500 mg / day,amoxicillin 1 g / day and the following 23 daysreceiving Omeprazole 20 mg / day, after whichshe was conducted to determine H. pyloriantigen in faeces, which turned negative. Therevaluation of white blood cell counts at 7 daysafter oral antistaphylococcal therapy andtreatment Anti H. Pylori, revealed normal values.A month later, at study entry, this patientreported, as figured below, a form of moderateacne, grade 4, residual lesions andhyperpigmented atrophic scarring, both on thefront neckline and upper limbs. The patientreceived therapy cleansing gel andmetronidazole and amazing seboregulator hasshown favorable response after 4 weeks oftreatment. In this particular situation of this case,in about 2 weeks after discontinuing the localtreatment, scar lesions reopened, turning intointense erythematous lesions, almost witherosion and without exudate, and acne lesionshad gradually reappeared evolving very fast (inabout 24 hours) from pimple to skin papule andlater atrophic scars remain more or less obviousor even residual hyperpigmented lesions. Thispatient, as shown above, was monitored aftertrial endind and we found out that in case ofrelapse, the symptoms disappear as fast as thefirst time (4 weeks), applying the same localtherapy, ie cleansing gel gel seboregulator andmetronidazole. Next, taking advantage of thedisappearance of acne lesions and erosive lesionsclose, patient received depigmentation creamtreatment (Neotone radiance), and chemicalpeeling. All topical treatments were applied toboth face and body, with similar results. Mentionthat the patient was not only veryconscientiously, but was also well documentedby its profession (family doctor).

36


b) Fotografii efectuate dupã 4 sãptãmâni de tratament cu gelul de curãþare, gelul seboregulator ºi metronidazol (menþionãm cãpacientul a fost tratat antiacneic pe jumãtate din faþã, cealaltã jumãtate fiind tratatã cu placebo)

b) photos taken after 8 weeks of treatment with cleansing gel and seboregulator gel (note that the patient was treated for acne onhalf of the face, the other half being treated with placebo)

a) Fotografii efectuate înainte de începerea tratamentului (faþã ºi profil dreapta ºi stânga)a) Fhotos taken before treatment (left and right front and profile)

37


c) Fotografii efectuate membrelor superioare iniþial ºi dupã 4 sãptãmâni de tratament local, cu asocirea gel de curãþare, gelseboregulator ºi metronidazol: - Fotografii efectuate înainte de începerea tratamentului

c) Photos of the initial upper limb and 4 weeks after local treatment with association of cleansing gel, seboregulator gel andmetronidazole:- Photos taken before treatment

- Fotografii efectuate dupã 4 sãptãmâni de tratament- Photos after 4 weeks of treatment

38


Cazul 2: Pacientã în vârstã de 29 ani, cu acneemoderatã gradul 3 tratatã cu gelul de curãþare ºigelul seboregulator. Aceastã pacientã a prezentatîn adolescenþã o acnee de tip polimorf, a avut osingurã încercare de tratament eºuat, din vinapacientei, care nu a respectat întocmai indicaþiilemedicului terapeut. Ca urmare, leziunile acneiceau persistat din adolescenþã pânã în prezent, cuvariate oscilaþii de intensitate. Aceastã pacientã aprezentat la examenul parazitologic perioralDemodex folliculorum prezent.

Case 2: 29 years old patient with moderateacne stage 3 treated with cleansing gel andseboregulator gel. This patient presented inadolescence multiforme type acne, had only onefailed treatment attempt, due to the fault of thepatient, not following phisician’s indications. Asa result, acne lesions persisted from adolescenceuntil now, with various intensity. Parasitologicalexamination revealed perioral Demodexfolliculorum.

a) Fotografii efectuate înainte de începerea tratamentului (faþã ºi profil dreapta ºi stânga)a) photos taken before treatment (left and right front and profile)

39


Cazul 3: Pacient, 18 ani, cu acnee moderatãgradul 4, evoluþie dupã 12 sãptãmâni detratament cu gelul de curãþare ºi gelul sebo-regulator. Pacientul prezintã acnee de la 15 ani, ºia efectuat haotic tot felul de monoterapii topice,cu eficienþã minimã.

Case 3: Patient, 18 years old with moderateacne stage 4, evolution after 12 weeks oftreatment with cleansing gel and seboregulatorgel. Patient has acne at 15 years, and made allsorts of chaotic topical monotherapy withminimum efficiency.

b) Fotografii efectuate dupã 8 sãptãmâni de tratament cu gelul de curãþare ºi gelul seboregulator (menþionãm cã pacientul a fosttratat antiacneic pe jumãtate din faþã, cealaltã jumãtate fiind tratatã cu placebo)

b) photos taken after 8 weeks of treatment with cleansing gel and seboregulator gel (note that the patient was treated for acne onhalf of the face, the other half being treated with placebo)

a) Fotografii efectuate înainte de începerea tratamentului (faþã ºi profil dreapta ºi stânga)a) Photos taken before treatment (left and right front and profile)

40


Bibliografie/Bibliography

1. Lucky AW, Biro Fm, Huster GA et al. Acne vulgaris in premenarchal girls. Arch Dermatol 1994; 130:308-14.2. Lucky AW, Biro FM , Huster GA et al. Acne vulgaris in premenarchal girls. Arch Dermatol 1994; 130:310-4.3. Cibula D, Hill M, Vohradnikova O et al. The role of androgens in determining acne severity in adult women.

Br J Dermatol 2000; 143:399-4.4. Bunker CB, Newton JA , Kilbom J et al. Most women with acne have polycystic ovaries . Br J Dermatol 1989;

121:675-80.

b) Fotografii efectuate dupã 12 sãptãmâni de tratament cu gelul de curãþare ºi gelul seboregulator (menþionãm cã pacientul afost tratat antiacneic pe jumãtatea din faþã, cealaltã jumãtate fiind tratatã cu placebo)

b) Photos performed after 12 weeks of treatment with cleansing gel and seboregulator gel (note that the patient was treated foracne on half of the face, the other half being treated with placebo)

41


5. Peserico A, Angeloni G, Bertoli P et al. Prevalence of polycystic ovaries in women with acne. Arch Dermatol Res1989; 281:502-3.

6. Ebling FJ. Hormonal control and methods of measuring sebaceous gland activity. J Invest Dermatol 1974; 62:161-71.

7. Imperato- MC Ginley J , Gautier T , Cai LQ et al. The androgen control of sebum production :studies of subjectswith dihydrotestosterone deficiency and complete androgen insensitivity . J Clin Endocrin Metabol 1993; 76:524-8.

8. Pochi PE, Strauss JS. Sebaceous gland response in man to the administration of testosterone D4-androstenedione and dehydroandrosterone. J Invest Dermatol 1969;52:32-6

9. Burton JL, Shuster S. The relationship between seborrhoea and acne vulgaris. Br J Dermatol 1971;84:600-1.10. Kligman AM, Katz AC. Pathogenesis of acne vulgaris . I. Comedogenic properties of human sebum in external

ear canal of the rabbit . Arch Dermatol 1968; 98:53-7.11. Tucker SB , Flannigan SA, Dunbar M et al. Development of an objectiva comedogenicity assay . Arch Dermatol

1986; 122:699-202.12. Zouboulis CC. Is acne vulgaris a genuine inflammatory disease? Dermatology 2001; 203:277-9.13. Holland DB, Jeremy AHT. The role of inflammation in the pathogenesis of acne and acne scarring. Semin Cutan

Med Surg 2005; 24:79-83.14. Lavker RM, Leyden JJ, McCineley KJ. The relationship between bacteria and the abnormal follicular

keratinization in acne vulgaris. J Invest Dermatol 1981; 77:325-30.15. Holland KT, Cunliffe WJ, Roberts CD. The role of bacteria in acne vulgaris- a new approach. Clin Exp Dermatol

1978; 3:253-7.16. Mourelatos K, Eady EH , Cunliffe WJ et al. Temporal changes in sebum excretion and propionibacterial

colonization in preadolescent children with and without acne. Br J Dermatol 2007; 156:22-31. 17. Ingham E. The immunology of Propionibacterium acnes and acne. Curr Opin Infec Dis 1999;12:191-7.18. Gribbon EM, Shoesmith JG, Cunliffe WJ, Holland KT. The microerophily and photosensitivity of

propionibacterium acnes. J Appl Bacteriol 1994; 77:583-90.19. Leyden JL, McGineley KJ, Milles OH et al. Propianibacterium levels in patients with and without acne vulgaris.

J Invest Dermatol 1975; 65:382-4.20. Ingham E, Holland KT, Gowland C et al. Studies of the extracellular proteolytic activity produced by

Propionibacterium acnes. J Appl Bacteriol 1983; 54:283-71.21. Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg 2001; 20:139-41.22. Jappe U, Ingham E, Henwood J et al. Propionibacterium acnes and inflammation in acne: P. Acnes t-cell

mitogenic activity. Br J Dermatol 2002; 146:202-9.23. Elman M, Lebyelter J. Light Therapy in the treatment of acne vulgaris. Dermatol Surg 2004; 30: 131-146.24. Dreno B, Poli F et al. Development and evaluation of a Global Acne Severity Scale (GEA Scale) suitable for France

and Europe. JEADV 2011; 25: 43-48.

Conflict de interese Conflict of interestNEDECLARATE NONE DECLARED

Adresã de corespondenþã: Aura VlãduþiCorresponding address: Tel./Phone: 0723-235.601

email: [email protected]

Intrat în redacþie: 2.12.2011 Received:2.12.2011

Documents

STUDII CLINICE ªI EXPERIMENTALE EXPERIMENTAL AND …bacteriilor (Propionilbacterium acnes) dezvoltate în mediul anaerob, intrafolicular ce întreþin inflamaþia prin compuºii de