Med Oral Patol Oral Cir Bucal. 2019 Jul 1;24 (4):e452-60. Oral mucosal peeling

Journal section: and Pathology doi:10.4317/medoral.22939 Publication Types: Review http://dx.doi.org/doi:10.4317/medoral.22939

Oral mucosal peeling related to dentifrices and mouthwashes: A systematic review

Daniel Pérez-López 1, Pablo Varela-Centelles 1,2, María J. García-Pola 3, Pablo Castelo-Baz 1, Lucía García-Caballero 1, Juan M. Seoane-Romero 3

1 Dept of Surgery & Medical-Surgical Specialities. School of Medicine & Dentristry. University of Santiago de Compostela. 2 CS Praza do Ferrol. EOXI Lugo, Cervo, e Monforte. Servizo Galego de Saúde. Lugo. Spain. 3 Dept of Surgery & Medical-Surgical Specialities. School of Medicine & Health Sciences. University of Oviedo. Spain.

Correspondence: CS Praza do Ferrol Praza Ferrol 11 27001 Lugo. Spain [email protected] Pérez-López D, Varela-Centelles P, García-Pola MJ, Castelo-Baz P, García-Caballero L, Seoane-Romero JM. Oral mucosal peeling related to dentifrices and mouthwashes: A systematic review. Med Oral Patol Oral

Received: 18/12/2018 Cir Bucal. 2019 Jul 1;24 (4):e452-60. http://www.medicinaoral.com/medoralfree01/v24i4/medoralv24i4p452.pdf Accepted: 13/03/2019

Article Number: 22939 http://www.medicinaoral.com/ © Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946 eMail: [email protected] Indexed in: Science Citation Index Expanded Journal Citation Reports Index Medicus, MEDLINE, PubMed Scopus, Embase and Emcare Indice Médico Español

Abstract Background: The aim of this systematic review was to summarise the clinical information available about oral mucosal peeling (OMP) and to explore its aetiopathogenic association with dentifrices and mouthwashes. Material and Methods: PICOS outline: Population: subjects diagnosed clinically and/or pathologically. Interven- tion: exposition to oral hygiene products. Comparisons: patients using products at different concentrations. Out- comes: clinicopathological outcomes (primary) and oral epithelial desquamation (secondary) after use. Study de- sign: any. Exclusion criteria: reports on secondary or unpublished data, in vitro studies. Data were independently extracted by two reviewers. Results: Fifteen reports were selected from 410 identified. Descriptive studies mainly showed low bias risk, ex- perimental studies mostly an “unclear risk”. Dentifrices or mouthwashes were linked to OMP, with an unknown origin in 5 subjects. Sodium lauryl-sulphate (SLS) was behind this disorder in 21 subjects, tartar-control denti- frices in 2, and flavouring agents in 1 case. Desquamation extension was linked to SLS concentration. Most cases were painless, leaving normal mucosa after desquamation. Tartar-control dentifrices caused ulcerations more frequently. Conclusions: OMP management should consider differential diagnosis with oral desquamative lesions, particu- larly desquamative , with a guided clinical interview together with pathological confirmation while discouraging the use of the product responsible for OMP.

Key words: Systematic review, oral mucosal peeling, dentifrices, sodium lauryl-sulphate, oral hygiene products.

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Introduction on 19 June 2018, together with ISI proceedings for both A possible relationship between oral des- English and non-English written articles. The search quamation and dentifrices was hypothesized in early was supplemented by scanning the reference lists of rel- 1970s by Pnacek (1), and very few cases have been re- evant review papers identified as well as those of the ported ever since (2-4), although oral mucosal peeling articles of finally included in this systematic review. We (OMP) induced by oral hygiene products seems to be a also explored the authors’ personal files to make sure relatively common finding in clinical practice (5). that all relevant material had been captured. Three au- Several agents have been linked to adverse oral mucosal thors were contacted for further information and all of reactions, but attention has focused on detergents, par- them attended our request (2,3,21). ticularly sodium lauryl sulphate (SLS) (3,6-10), which The search was updated on 8 November 2018. Search has been reported to induce OMP together with muco- strategy: ((“mouth mucosa”[MeSH Terms] OR sal inflammation, higher permeability to chemicals, and (“mouth”[All Fields] AND “mucosa”[All Fields]) OR denaturation of proteins (11). Neither the aetiopathogen- “mouth mucosa”[All Fields] OR (“oral”[All Fields] AND esis of OMP nor its clinicopathological features are well “mucosa”[All Fields]) OR “”[All Fields]) established (11-15). It is often unrecognised because its AND (peeling[All Fields] OR shedding[All Fields] asymptomatic nature results in some patients deciding OR epitheliolysis[All Fields] OR desquamation[All to ignore it while others are distressed because clini- Fields])) OR (((“toothpastes”[MeSH Terms] OR cians are sometimes unable to identify a cause or to “toothpastes”[All Fields] OR “toothpaste”[All Fields]) establish treatment (11,16). However, -and considering OR (“dentifrices”[Pharmacological Action] OR differential diagnoses of OMP include erosive oral dis- “dentifrices”[MeSH Terms] OR “dentifrices”[All Fields]) orders such as , autoimmune alterations, OR (“mouthwashes”[Pharmacological Action] OR candidosis, mechanical, thermal or chemical trauma, “mouthwashes”[MeSH Terms] OR “mouthwashes”[All adverse drug reactions, viral infections, and recurrent Fields])) AND ((“adverse effects”[Subheading] OR aphtous ulcerations- establishing a definitive diagnosis (“adverse”[All Fields] AND “effects”[All Fields]) OR is paramount (11,17). “adverse effects”[All Fields] OR (“side”[All Fields] In this situation, where the aetiopathogenesis is poorly AND “effects”[All Fields]) OR “side effects”[All understood, the clinical presentation is often unrec- Fields]) OR (“adverse effects”[Subheading] OR ognised, the diagnosis and treatment are not soundly (“adverse”[All Fields] AND “effects”[All Fields]) founded, along with the lack of previous reviews on this OR “adverse effects”[All Fields])) AND (“mouth topic justify the need for a systematic review on the rela- mucosa”[MeSH Terms] OR (“mouth”[All Fields] AND tionship of OMP with the use of dentifrices and mouth- “mucosa”[All Fields]) OR “mouth mucosa”[All Fields] washes. Thus, the aim of this systematic review was to OR (“oral”[All Fields] AND “mucosa”[All Fields]) OR summarise the clinical information available about oral “oral mucosa”[All Fields])) mucosal peeling and to explore its aetiopathogenic as- -Eligibility criteria sociation with dentifrices and mouthwashes. Inclusion: clinical and experimental reports address- ing OMP induced by dentifrices and mouthwashes. No Material and Methods limitations by language or publication date were intro- The review protocol was agreed by all authors and regis- duced. Exclusion: papers reporting on secondary data, tered with the International Prospective Register of Sys- in vitro studies, and unpublished data. tematic Reviews (PROSPERO, No: CRD42018103792) -Data collection and extraction (18). This systematic review was performed according Data extraction was independently performed by two to the PRISMA (Preferred Reporting Items for System- reviewers (DPL & PVC) and results summarized in atic Reviews and Meta-analysis) guidelines (19) and fol- standardized forms for descriptive and experimental lowed the outlines of PICOS (20): i) Population: subjects studies. Inter-observer concordance was calculated us- clinically and/or pathologically diagnosed of OMP; ii) ing the Epidat 3.1 statistical package (Programa para Intervention: exposition to oral hygiene products; iii) Análisis Epidemiológico de Datos Tabulados. Xunta Comparisons: patients using different dentifrices and de Galicia. Santiago de Compostela. Spain). Reports mouthwashes at different concentrations under experi- identified through the searches were exported to Ref- mental conditions; iv) Outcomes: primary outcome: works (ProQuest, Santiago de Compostela, Spain) and clinical and histological outcomes after using dentifric- checked for duplicates. Papers were filtered by title and es and mouthwashes. Secondary outcome: desquama- the relevant ones retrieved for further analysis. The rea- tion of oral epithelium after exposition to oral hygiene sons for exclusions were recorded at each step. products; v) Study design: any type. Data retrieved for descriptive studies included: authors -Information sources and systematic search and year of publication, study type, number of partici- Medline (PubMed) and Embase (Ovid) were searched pants, age, gender, medical and dental history, medica-

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tion, oral hygiene products, symptomatology, site of the siders 4 specific dimensions: selection, ascertainment, lesion, evolution time, diagnostic methods, histopatho- causality, and reporting. The risk for bias was grouped logical findings, and management. In the case of experi- under the following categories: Low risk: low risk of mental studies, the following information was recorded: bias for all domains; Unclear risk: unclear risk for one authors and year of publication, study type, number of or more domains; and High risk: high risk for one or participants, inclusion / exclusion criteria, age, gender, more domains. Quality was independently assessed by exposition variable / oral hygiene products, result vari- two reviewers (DP & PV), who solved disagreements able / adverse effects, site of the lesion, study periods, by discussion until a consensus was reached. and diagnostic methods. -Quality assessment Results The Cochrane Collaboration´s tool for assessing risk -Study selection of bias was used for experimental studies (22), which We identified 713 potentially eligible reports, and 646 includes 7 dominions: Random sequence generation remained after adjusting for duplicates. Another 341 (selection bias), allocation concealment (selection bias), of them were discarded after checking their abstracts blinding of participants and personnel (performance (kappa= 0.659). The full texts of the remaining 20 re- bias), blinding of outcome assessment (detection bias), ports were retrieved and examined. As a result, 11 re- incomplete outcome data ( bias), selective re- ports were selected (Kappa= 0.813). Four additional porting (reporting bias), and other sources of bias. Case papers were identified by screening the reference lists reports and case series was evaluated by means of the of these reports, so a total of 15 articles were finally instrument proposed by Murad et al (23), which con- included in this systematic review (Fig. 1).

PRISMA 2009 Flow Diagram

Records identified through

database searching (n = 713) Embase: n = 130 PubMed: n = 583 ISI Proceedings: 0

Identification

Records after duplicates removed (n = 646)

Screening Records excluded for not Records screened fulfilling the inclusion (n = 646) criteria (n = 620)

Full-text articles excluded Full-text articles assessed (n = 15: 1 review, for eligibility 14 other objectives or (n = 26) Eligibility lesions)

Included articles (n = 11)

Additional articles from

Included reference list checking (n = 4)

Studies included in qualitative synthesis (n = 15)

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta- Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097

For more information, visit www.prisma-statement.org. Fig. 1: PRISMA flow diagram.

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-Risk of bias in included studies Fungal staining was performed in 6 incisional Descriptive studies were mainly found to be at a low (3,4,2425,25) and 7 peeling (3). All were nega- risk (2,3,6,11,24,25), as only three papers scored a high tive but one surgical specimen that showed PAS-posi- risk for bias (4,5,16). Regarding experimental studies, tive material within the epithelium, but no yeast forms five reports were classified as “unclear risk for bias” were seen (25). (7,21,26,27), and the other two selected papers were The main treatment of OMP induced by oral hygiene found to be at high (28) and low (29) risk respectively. products was discontinuation of the causal toothpaste or -Descriptive studies mouthwash (2,3,5,6,24,25), sometimes accompanied by Six case reports (5,6,16,11,24,25) and 3 case series (2-4) the use of a regular (5,24) or biologically inert dentifrice were selected (Table 1), all published in English but one, (25). Resolution time ranged between 24 hours and 3 in German. Most papers were authored in the States -6 weeks (2,3,6). papers (4-6,11,24,25)-. The remaining reports came -Experimental studies from Germany (3), Jordan/United Kingdom (16), and Six articles involving 7 experimental studies were fi- Italy (2). nally selected for the review (7,21,26-29). All were The selected descriptive studies reported on 28 sub- published in English: three papers came from Norway jects, mostly -20- females. Age ranges varied from 47- (7,21,29) and 3 from the USA (26-28) (Table 2). 72 years for 6 subjects (3), to 27-80 (2,4-6,16,24,25), Toothpaste studies mainly consisted of two methodolo- with an average of 49.5. gies: three studies applied a toothpaste-containing cap Systemic conditions were reported for 6 individuals splinted to the upper jaw during 2 minutes, twice a day who were under medication, although these drugs were for 4 days (7,21,29), while another study employed the rather heterogeneous and not consistent among case same method for 5 minutes, once a day for 5 days (7) In reports (4,6,25,26). Dentifrices or mouthwashes were addition, 2 more studies asked subjects to brush their found to be related to this phenomenon in 23 individu- teeth for 2 minutes, 3 times per day for 2 weeks (26,27). als (2,3,5,6,24,25), while the causal agent could not be The mouthwash study design consisted of a supervised identified in 5 subjects (4,16). Histopathological char- 30-second rinsing plus homemade rinses for the same acteristics (3,4,6,24,25) and management strategies (2- time, 3 times a day for 2 weeks (28). 6,16,24,25) were described in 25 cases. Most studies focused on dentifrice adverse effects Most subjects were affected by painless OMP showing on oral mucosa, mainly desquamation -6 out of 7- otherwise normal mucosa after desquamation (23/28). (7,21,26,27,31), while mouthwashes were investigated In addition, 2 case reports described the same symp- in a single report (28). The most frequently examined tomatology without providing data about the remaining ingredient was 0.25-3 % SLS -4 out of 6- (7,21,29). Es- tissue after desquamation (5,24). Painful erosions after sential oils were analysed in the mouthwash study (28). peeling were present in the remaining 3 subjects (3,6), Four studies have demonstrated a causal relationship who reported burning or dry mouth sensation in two between SLS-containing toothpastes and OMP, even (5,24) and one (25) individuals, respectively. at low concentrations (7,21,29). SLS in concentrations OMP was linked to SLS toothpastes in 21 subjects of 0.5 %, 1.0 %, and 1.5 % were responsible for 13/37, (2,3,6,24,25), while tartar control dentifrices were asso- 20/37 and 51/75 oral mucosal desquamations, respec- ciated to another 2 cases (5,24), where flavouring agents tively (7,21,29). were held responsible in one of them (24). Differences in the occurrence of OMP between 1.5 % Lesions were most frequently located in the alveolar SLS and detergent-free toothpastes resulted significant mucosa, vestibules and buccal mucosa (2,4,6,16,24,25). in one study (7), while other investigation reported this Seven patients showed widespread lesions throughout difference even with 0.5 % SLS dentifrices (29). the oral cavity (3). Additionally, SLS toothpastes have been significantly The time of OMP evolution varied from 3 days to 10 related to higher incidence of OMP when compared to years. This information was missing for 3 subjects (4-6). the alternative detergent cocoamidopropyl-betaine (29). Incisional and peeling biopsies were performed in 7 Furthermore, the extent of desquamation has been sig- (3,4,6,24,25) and 19 (2-4) subjects, respectively. The nificantly linked to SLS concentration. In this vein, two former usually revealed a superficial intraepithelial studies grading the severity of OMP have shown tooth- linear cleft accompanied by parakeratosis, mild acan- pastes with 1.5 % SLS were responsible for 14/55 isolat- thosis, intracellular oedema, normal connective tissue, ed and 24/55 widespread desquamative reactions (7,29). and negative direct immunofluorescence. Peeling biop- The addition of triclosan in concentrations of 0.3 % has sies showed an epithelium composed of 2-15 layers with been demonstrated to significantly reduce the number thin elongated strips of parakeratotic material and some of desquamative reactions compared to 1.5 % SLS as polyhedral squamous cells with lightly stained cyto- well as their severity with 3 % SLS (7). plasms; nor dysplasia nor vesicles were present. On the other hand, a stannous fluoride dentifrice has

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methods

tic saliva Microscopic Photographs Photographs Photographs Photographs Photographs Microscopic collected saliva collected Oralexploration Oralexploration Oralexploration Oralexploration Oralexamination Oralexamination Oralexploration Epithelial flakes in assessment of flakes Epithelial flakes in assessment of flakes Diagnos

:

;

free TP) free TP) free TP )

- -

twice daily, twice brushing with with brushing free TP 1 weekfree flossing) flossing) (brushing with

-

brushing

o water) free TP 4 weeks free water) 2 weeks ; n - periods ( periods

flossing) (except for flossing) for (except (except for (except 2 minutes, 3 times2 minutes, daily,

Study periods Study saline solution) days 2 minutes, twice daily, 4 days; 4 days; daily, twice 2 minutes, Dental prophylaxis Dental Dental prophylaxis Dental 4 Baseline examination Baseline resting week brushing with water with brushing week 2 minutes, 3 times 2 weeks daily, 2 minutes, - y resting periods y resting

o OH (except for o OH o breath freshening products) freshening breath 1 Detergent n n No OH No da week resting period (control (control period resting week day resting periods (brushing with with (brushing periods resting day - Brushing no oral hygiene (except for dental dental for (except hygiene no oral day resting periods (detergent periods resting day (detergent periods resting day week Cap splints 2 minutes, Cap splints 2 - 10 - 0 seconds, 3 times daily, 14 days; usual usual 14 days; daily, 3 times 0 seconds, diet and oral hygiene (no other MW other (no or hygiene oral and diet week resting periods (usual oral hygiene) oral (usual periods resting week 10 - 1 3 - 10 - 10 - TP C 4 weeks; detergent Cap splints 5 minutes, once daily, 5 days once daily, 5 minutes, Cap splints 1 Supervised rinsing for 30 seconds + rinsing + rinsing 30 seconds for rinsing Supervised Cap splints Cap splints Cap splints 2 minutes, twice daily, 4 days daily, twice 2 minutes, Cap splints Brushing

NR NR Buccal mucosa Lesion Lesion location Cap splint Cap splint Cap splint Cap splint

: :

*) % TP *)

E and

-

tongue MP +

*)

,C

TP D and control and OMP OMP OMP

*) E control and ) isolat ed E - - (TP B*)(TP

(TP C*)(TP OMPulcerations +

(TP B ; 10/92 O 10/92 ;

.

OMP( e / adversee / effects % detergent, no tartar no tartar % detergent,

0.45 TP*: (control (TP D isolated isolated isolated isolated isolated isolated

(TP D 4/10 OMP4/10 OMP6/10 1/75 OMP1/75 OMP3/10 OMP2/18

3/75 OMP3/75 OMP4/10 OMP0/10 OMP0/18 control* : 3/92 OMP 3/92 : ulcerations (stannous fluoride (stannous P ; 9/93 : : : : : :

C B B B: B: C D A A A: 1/27 1/27 1/27 1/27 1/27 1/27 7/10 OMP7/10 isolated isolated 2/28 OMP:2/28 2 variabl widespread 8 isolated, 9 widespread8 isolated, F: widespread E: D: 8 isolated, 8 widespread8 isolated, A: 21/28 OMP: 6 isolated, 15 OMP:21/28 6 isolated, 19/28 OMP: 12 isolated, 7 OMP:19/28 12 isolated, C: 6/92 OMP6/92 9/27 9/27 control agents) control 1/75 OMP,1/75 OMP 1/75 + A: 17/27 OMP17/27 B: : 16/27 OM16/27 3/92 OMP3/92 : A Result A: : C C: flavouring, 0.60 flavouring, B: B inflammation

%

giene te TP

betaine TP betaine TP betaine TP - - - 3.3 detergent, TP

TP

TP

% free TP -

TP products citrate TP variable / oral h y oral / variable 1.5% SLS TP 1.5% SLS TP 1.5% SLS TP 0.5% 1.5% SLS TP 1.5% 1.0% SLS TP 1.0% SLS TP 1.5% 0.5% SLS SLS TP 1.0%

0.25% SLS : : : essential oil MW detergent :

control agents control pyrophosphate TP pyrophosphate TP pyrophosphate B B: C: C D A: A: A: A 5% hydroalcohol MW 5% hydroalcohol A: C: SLS, 0.3% triclosan, 0.75% zinc

B: 1.2 % flavouring, sodium monofluorophospha 0.64% cocoamidopropyl 1.27% cocoamidopropyl : 1.90% cocoamidopropyl 1.5% 1.15% flavouring, 1.2% detergent, 3.3% 1.2% detergent, 1.15% flavouring, 0.95

A Intervention : 0.95% flavouring, 1.2% detergent, no tartar no tartar 1.2% detergent, 0.95% flavouring, whitener/ brightener/flavour enhanced TP enhanced brightener/flavour whitener/ : F: E: whitener/ brightener/ flavour enhanced TP enhanced flavour brightener/ whitener/ D: 3% SLS, 0,3% triclosan, 0,75% zinc citrate

B: : : B : A C C B B:

M/F 0/24 NR 0/10 0/10 0/27 0/18 5 28/64 Gender

71 76 31 48 65 63

(47) (61) Age (25) (40) 24 - 45 - 20 - 21 - 30 - 22 - (27.6) (mean)

92 ) 27 18

n smokers 18 → ( - 74 10 10 28 → → ≥ Subjects Healthy Healthy Healthy 28 21 Nodrugs Nodrugs No OMD No OMD No OMD No OMD No No OMD No 107 Xerostomia Availability Nogingivitis 18 non Noradiotherapy Noperiodontitis ------

nd, nd, sover server - type study study study study study study study blind, blind, blind, blind, blind, blind, blind, blind, bli Study Study Double Double Double Double Double Double crossover crossover crossover crossover crossover cros crossover Ob

Data extraction for experimental studies.

et et et et 21 ) 29 ) ( (

, 2004 ,

year ) ) , 1973 , 1990 , 1996 , 1996 , 7 7 Authors, Authors, 26 ) 27 ) a b 28 ) ( ( ( ( and and Barkvoll, 1996 Kowitz al. Kowitz al. Herlofson and Barkvoll, 1993 Skaare al. Skaare al. Herlofson Fischman et al. ( Table 1: female; mouthwash; M: male;F: MW: NR: not reported; OMD; oral mucosal diseases; OMP: oral mucosal peeling; sodium SLS: lauryl sulphate; TP: toothpaste statistically*: significant

e456 Med Oral Patol Oral Cir Bucal. 2019 Jul 1;24 (4):e452-60. Oral mucosal peeling

-

19

-

)

NR NR NR days (unresolved) Oralnystatin Management healing after 2 Discontinuing TP Discontinuing TP Discontinuing ( (healing after 1 week) after (healing

,

ial

; ormal o 15 layers - cells with

, negative , egative IgG, n

; for Candida for

edeman , o keratinocytes ormal connective ntracellular

staining fungal and

orizontal intraepithel , horizontal , cleft, mild h

is and epithelial is edema, n ; inear intraepithelial cleft intraepithelial l inear , IgA o fungal staining fungal intracellular intracellular , negative fungal staining fungal negative , ome polyhedral squamous cells squamous cells ome polyhedral tion of epithelium maturation epithelium of tion r testing: negative , s , acantholysis; i acantholysis;

findings Histopathological o withlight staining cytoplasms tissue Large and irregular C3, IgM, ; n Parakeratosis Altera Smea ild acanthos ild Thin elongated strips of parakeratotic without dysplasia or vesicles or dysplasia without Parakeratosis m intracellular intracellular Parakeratosis acanthosis, acanthosis, ormal mesenchymal tissues material , negative fungal staining fungal negative , connective tissue : epithelium Peeling with 2 n cleft

methods biopsy

tic Anamnesis Anamnesis Anamnesis Anamnesis Smear testing Peeling biopsy Peeling ncisional biopsy ncisional Peeling biopsy Peeling Peeling biopsy Peeling I Fungal cultures Fungal Oralexploration Incisional Incisional biopsy Incisional Oralexamination Oralexamination Oralexamination Oralexamination Incisional biopsies Incisional Diagnos

4

- 18 22 2 NR Time Days/ weeks months months months months Several

location

mucosa

propria ip mucosa ip entral tongue entral L L uccal mucosa uccal mucosa Widespread Mouth floor Oralvestibule V B B Lesion Including gingiva gingiva Including

tous

rosions OMP e NMB NMB NMB NMB tissue NMB NMB 5 ainless OMPainless eukoedema painful P Painless OMP Painless OMP Painless OMP Painless Painless OMP L 2 Symptomatology

TP

STP TP

+ + giene Not Not Not Not Oral y roducts 10% SLS fluoride h - Stannous Stannous p identified identified identified identified 2% SLS 5 1.

NR NR Buspirone Lovastatin Medication hydrochloride hydrochloride Not remarkable Not Chlorpromazine

, ,

leostomy

rolemia

local trauma local chizophrenia

o local trauma NR , s , o medication o medication , no no , n , history lacement Healthy p “Light” smoker Nolocal trauma smoker, no traumatic - habits, n Hypercholeste o medication placement Unremarkable medical Unremarkable no aspirin placement, no placement, no aspirin Ex n Depression Medical and dental history and dental Medical Ulcerativecolitis, i Notobacco Notobacco peculiar reactions to TP/MW

/

12 72 /

1M 6F 4M ±

67/F 56/F 55/F 45 - Age/ 31/ 33/M 49 gender 7F

) n (4) (7) ( CS CS CS (11) Study type Study Data extraction for descriptive studies.

) )

et 4 3

( (

, 2017 ,

) Authors, Authors, year 2 al. Zegarelli and Silvers, 1994 Plonait and Reichart, 1999 Berton

( Table 2: CS: case series; females; F: M: males; MW: mouthwash; NMB: normal mucosalphosphate; base; TP: toothpaste NP: not performed; NR: not reported; OMP: oral mucosal peeling; SLS: sodium lauryl sulphate; STP: sodium tripoly

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been reported to produce a significant lower level of thelial cells from irritation and inhibiting the cascade oral adverse reactions (desquamation, ulceration, in- of inflammatory reactions (7,32). Zinc may also have a flammation and erythema) than whitener/brightener/ stabilizing effect on the mucosa (33). Additionally, al- flavour-enhanced, sodium fluoride toothpastes (26). terations in oral mucosal permeability and absorption Tartar control toothpastes have been associated with a with age may be explained by differences in mucosal re- higher number of ulcerations, sloughing, and erythema sponse to SLS in pre- and post-menopausal women (34). than dentifrices including the same concentrations of Apart from that, the concomitant effect of other ingre- flavourings and detergents but without pyrophosphate dients, such as stannous fluoride or sodium tripolyphos- (27). This latter report focused on desquamation found phate, require further investigation (2,35). The part of a significant difference only between a dentifrice con- tartar control agents in OMP and the possible role of taining 3.3 % pyrophosphate and a toothpaste without flavourings also needs to be elucidated (24,27). tartar control agents (27). -Clinical appearance OMP induced by oral hygiene products usually dis- Discussion plays a grey-whitish strips of oral epithelium that either The limitations inherent to the reduced number of pa- slough spontaneously or can be easily peeled off expos- tients reported in uncontrolled and retrospective case ing an otherwise normal tissue (3-5,16,24,25) (Fig. 2). reports/case series requires a cautious interpretation of Occasionally, this mucosa shows a whitish colour simi- their data. However, experimental studies, mainly at lar to (4,25). This condition is frequently low or unclear risk of bias, provided information robust asymptomatic but painful erosions after peeling may enough to state OMP induced by oral hygiene products also be present (3,6). is mainly linked to SLS-containing dentifrices, followed There is no gender or age pattern, although it is slightly by tartar-control formulations (3,5-7,21,24-27,29). more frequent among females in their 50s. No specific It is worth mentioning the wide variety of terms used to medical or dental conditions could be related to OMP designate this clinical condition: desquamative stomati- (2-6,16,24,25). Although various oral sites are usually tis (6), oral mucosal desquamation (2,21,29), oral slough affected, most frequently involved areas include oral (25), and shedding oral mucosa (4), but the term “oral vestibule, buccal mucosa and gingiva. The evolution mucosal peeling” (OMP) is the one which gathers the time is quite variable, from 3 days to 10 years, depend- largest proportion of cases and has gained acceptance ing on the exposition to the causal agent (2-6,16,24,25). within the scientific community (3, 16). -Histopathological features -Aetiopathogenesis Studies relying on incisional biopsies have shown a con- It has been stated that higher portions of anionic deter- stant pathological pattern for OMP characterized by a gents are likely to break up the intercellular structure of parakeratotic epithelium, mild acanthosis and intracel- the epithelium causing increased epithelial cell desqua- lular oedema. A linear, horizontal intraepithelial cleft mation, thus suggesting a toxic reaction in the genesis of without acantholysis can also be observed together with OMP (6,10). In fact, the peeling phenomenon has found absent or minimal inflammation of connective tissue. to be analogous to that in certain thermal of chemi- Negative direct immunofluorescence and fungal posi- cal injuries, such as aspirin burn, but in a milder form tive staining can usually be observed (3,4,6,24,25). (4,24). Our results show SLS, even at concentrations as -OMP as low as 0.25%, is related to the occurrence of desqua- Gingival desquamation, as a single location or associ- mation with a dose-response effect. Moreover, the dif- ated to desquamation of alveolar mucosa, lateral, ven- ferences in irritative potential between SLS and other tral or dorsal tongue, inner mucosa, floor of the detergents may be partially explained by the stronger mouth, vestibules and buccal mucosa, has been widely protein denaturation effect of anionic detergents (15). described in the realm of OMP (3,5,6,25). Thus, OMD Different critical micellar concentrations, adsorptive complies with the criteria for desquamative gingivitis properties, and effects on the biomembrane system have (DG) but this entity neither is a specific disorder nor has been also described as responsible for these variations a single aetiopathogenia. DG represents a wide group of (12-14), together with an influence of pH (3,6). mucocutaneous and systemic pathologies with gingival Undiluted SLS-containing toothpastes can be retained involvement (35-38), mainly pem- in the oral cavity after brushing with biological effects phigoid (MMP), oral lichen planus, and vul- of SLS for at least 2 hours after toothbrushing (30), but garis (35-38), but including also , with only minimal adverse oral mucosal reactions (31). graft-versus-host disease, , chronic Interestingly, triclosan has been demonstrated to reduce ulcerative , , linear IgA the number of desquamations and their severity by re- disease, dermatitis herpetiformis, epidermolysis bul- ducing the penetration of SLS molecules through the losa, paraneoplastic forms, psoriasis, and foreign body mucosa, stabilizing and protecting the superficial epi- gingivitis, together with drug induced forms (37,38) in

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Fig. 2: 1A: Epithelial desquamation in alveolar mucosa; 1B: Peeling biopsy technique in the inner side of lower lip: 2A: Parallel sheets of flattened surface layers corresponding to normal gingival stratified squamous epithelium (HE x4); 2B: At greater magnification, cells exhibited good maturation with round/elliptical to flattened nuclei of the superficial cells (HE x40).

minor frequencies. A reasonable addition to this already tensively used to reach a definitive diagnosis of OMP large list of disorders grouped under the heading of DG (3,4,6,24,25), although similar certainty in diagnosis would be OMP. can be achieved by peeling biopsy (3,4) (Fig. 2). A definitive diagnosis of DG requires a thorough clini- OMP does not require any kind of treatment beyond the cal examination including specific blood tests and, fre- discontinuation of the responsible toothpaste or mouth- quently, pathologic and immunopathologic assessments. wash when the peeling phenomenon causes discomfort In this vein and considering that clinical signs and (2,5,6,16,24,25). symptoms are insufficient to establish a definitive- di Clinical practitioners are in an advantageous position in agnosis, the stab-and-roll biopsy technique would make the prescription of oral hygiene products and, therefore, an important contribution to pathological diagnosis pre- in the diagnosis of this disorder. Awareness of OMP per- serving gingival epithelium in the specimen, which is mits a rapid and costless differential diagnosis with other crucial for an accurate DG diagnosis (35). DGs. Besides, the use of a peeling biopsy technique en- However, considering peeling biopsy technique can sures diagnosis in a more respectful way to the periodon- harvest enough epithelium for both pathological and tium than alternative, incisional biopsy techniques. immunofluorescence studies, it could be a sound alter- native -with less morbidity- to reach a definitive diagno- Conclusions sis of the cause behind DG. In non-conclusive cases, an With the limitations inherent to the type of studies in- incisional biopsy should be undertaken (36). cluded in this systematic review, it can be concluded -Diagnosis and management of OMP that there is a causal relationship between toothpastes Diagnosis of OMP is based upon a comprehensive intra- and mouthwashes with oral mucosal peeling, mostly oral exploration and also on a clinical interview focused due to high concentrations of sodium lauryl sulphate in at identifying topical substances -including oral hygiene their formulations, although other components of oral products- with a potential to induce desquamative oral hygiene products can also be held responsible for this lesions (37,38). In addition, and once a clinical judge- disorder in much lower frequencies. ment was established, an “ex juvantibus” approach Clinical management of OMP should consider differ- could also be attempted by discontinuing the use of the ential diagnosis with other oral desquamative lesions, potentially involved products. particularly DG, and include a guided clinical interview Peeling and incisional biopsies, as well as smear test- together with pathological confirmation through peel- ing, are the most frequently used diagnosis methods ing biopsy along with discouraging the use of the prod- (2-6,16,24,25). Incisional biopsies have been also ex- uct responsible for OMP.

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