Presence of streptococci and frequent tonsillitis among adolescents with psoriasis

Dear Editor, Many dermatologists may appreciate the role that tonsillar infections with Streptococcus pyogenes play in exacerbating or triggering their patients’ psoriasis. Especially relevant is the role of tonsillar streptococcal colonization in guttate psoriasis and in some cases in plaque psoriasis.1, 2 Perianal streptococcal infection has been observed in guttate psoriasis.3 Several biological mechanisms are suspected, among which the production of superantigens, overactivation of T cells and excessive cytokine release may be common to guttate and plaque psoriasis.4 Nevertheless, few studies have investigated whether colonization with streptococci and tonsillitis are implicated in paediatric psoriasis. In a study from the Danish National Birth Cohort (DNBC), we found that tonsillitis, especially streptococcal and recurrent tonsillitis, may play a role in paediatric psoriasis.5 In a smaller clinical subsample of the DNBC – the Psoriasis in Adolescents (PIA) cohort6 – we were able to investigate tonsillar and perineal carriage of various streptococci. The PIA cohort is a clinical case–control population nested in the DNBC and consisting of 315 adolescents (see Blegvad et al. for further information).6 Briefly, in 2016–2017, age‐ and sex‐matched cases of psoriasis and controls with and without parental psoriasis from the DNBC were invited to participate in a clinical study. Potential cases were identified based on maternal reports of psoriasis from responses to questionnaires in the DNBC at around child age 11 years. Additionally, two control groups were identified: with and without parental psoriasis (‘genetically disposed’ controls and ‘undisposed’ controls). Cases of psoriasis and corresponding genetically disposed and undisposed controls were confirmed following a thorough dermatological examination supported by evaluation of standardized diagnostic criteria.7 Participants were reclassified into their appropriate categories if the maternal reports of psoriasis were not confirmed upon clinical examination or revisions of family history revealed paternal or maternal psoriasis in the controls. The tonsils and perineum were swabbed for microbiological cultures and analysed at the Department of Clinical Microbiology at Herlev and Gentofte Hospital. The following bacteria were identified: S. pyogenes (group A), Streptococcus dysgalactiae (groups G and C) and Streptococcus agalactiae (group B). Self‐reported questionnaire data on tonsillitis and tonsillectomy were collected by interview. Two questionnaire items addressed self‐reported tonsillitis: one addressed whether the adolescent had ‘frequent tonsillitis’ and the other the specific number of episodes within the last 3 years (which we refer to as ‘recurrent tonsillitis’). For the latter, a cutoff of three or more episodes was chosen. Tests for between‐group differences of continuous and categorical data were performed using Student’s t‐test and Fisher’s exact test, respectively. We considered results with P < 0·05 significant. Analyses were performed using SAS statistical software, version 9·4 (SAS Institute Inc., Cary, NC, USA). Study approval for PIA was granted by the National Committee on Health Research Ethics (protocol no. H‐15004238) and the Danish Data Protection Agency (GEH‐2015‐071 I‐Suite no. 03641). Contrary to expectations, tonsillar carriage of S. pyogenes was similar among cases and genetically disposed and undisposed controls (0%, 1·8% and 3·3%, respectively; Table 1). Likewise, no significant differences in tonsillar or perineal carriage of S. agalactiae or S. dysgalactiae were detected, although carriage of these strains was more prevalent among cases. In contrast to analyses of data from microbiological cultures, self‐reported tonsillectomy and frequent tonsillitis were more frequently reported among adolescents with psoriasis (11%) than among undisposed controls (2·4%) (Table 1). Microbiological cultures, tonsillitis and tonsillectomy among cases of psoriasis and genetically disposed (GD) and undisposed controls The data are given as n (%), unless otherwise specified. NA, not applicable. There were two missing reports on tonsillar cultures for controls, two missing reports on perineal cultures for cases and three for controls, and one missing response to tonsillectomy. aStudent’s t‐tests were performed to test for group differences in means; Fisher’s exact tests were performed to test for group differences in proportions. GD tests compared cases with GD controls, while controls tests compared cases with undisposed controls. Microbiological cultures, tonsillitis and tonsillectomy among cases of psoriasis and genetically disposed (GD) and undisposed controls The data are given as n (%), unless otherwise specified. NA, not applicable. There were two missing reports on tonsillar cultures for controls, two missing reports on perineal cultures for cases and three for controls, and one missing response to tonsillectomy. aStudent’s t‐tests were performed to test for group differences in means; Fisher’s exact tests were performed to test for group differences in proportions. GD tests compared cases with GD controls, while controls tests compared cases with undisposed controls. Our results suggest that adolescents with psoriasis are not more likely to be carriers of S. pyogenes than their peers. Nonetheless, they are more likely to report recurrent tonsillitis, which is in line with our previous findings, but may be due to information bias.5 Interestingly, the proportion of genetically disposed controls with recurrent tonsillitis was intermediate to that of cases and undisposed controls. The HLA‐Cw*0602 allele may increase the risk of both psoriasis and streptococcal tonsillitis, which may explain this observation.8 Lack of streptococcal carriers of S. pyogenes among cases of psoriasis runs contrary to our own expectations, and certain explanations may be plausible. The most obvious of these is that cases – as our data suggest – are more likely to undergo a tonsillectomy, thereby reducing the risk of future streptococcal colonization. In this context, a tonsillectomy may be a result of recurrent tonsillitis and may serve as a disease severity modifier. Lastly, S. pyogenes is known to create biofilms, leading to negative cultures even in the presence of colonization. Carefully taken samples and microbiome analyses may provide a clearer picture in future studies. Differences between our study and that of Mallbris et al.8 deserve attention, but are likely explained by differences in time from disease onset. Jonathan Groot: Conceptualization (equal); Data curation (lead); Formal analysis (lead); Methodology (lead); Project administration (lead); Software (lead); Visualization (lead); Writing‐original draft (lead); Writing‐review & editing (lead). Christoffer Blegvad: Conceptualization (equal); Data curation (equal); Formal analysis (supporting); Funding acquisition (equal); Investigation (equal); Methodology (supporting); Project administration (equal); Software (supporting); Supervision (supporting); Validation (equal); Writing‐original draft (equal). Anne‐Marie Nybo Andersen: Conceptualization (equal); Data curation (supporting); Formal analysis (equal); Funding acquisition (equal); Investigation (supporting); Methodology (equal); Project administration (equal); Resources (lead); Supervision (supporting); Validation (equal); Visualization (supporting); Writing‐original draft (equal); Writing‐review & editing (supporting). Claus Zachariae: Conceptualization (supporting); Data curation (supporting); Formal analysis (supporting); Funding acquisition (equal); Investigation (supporting); Methodology (supporting); Resources (equal); Writing‐original draft (supporting). Jens Otto Jarløv: Conceptualization (supporting); Data curation (supporting); Formal analysis (equal); Funding acquisition (equal); Investigation (supporting); Methodology (equal); Resources (equal); Writing‐original draft (supporting). Lone Skov: Conceptualization (lead); Data curation (supporting); Formal analysis (equal); Funding acquisition (equal); Investigation (lead); Methodology (equal); Project administration (lead); Resources (lead); Supervision (lead); Validation (equal); Visualization (supporting); Writing‐original draft (equal); Writing‐review & editing (supporting). Funding sources: a grant from the LEO Foundation and the Danish Dermatological Society. The LEO Foundation and the Danish Dermatological Society were not involved in any portion of the study design, data collection, data analysis, manuscript preparation or review process, or in the decision to submit the manuscript for publication. Conflicts of interest: J.G., C.B., A.M.‐N.A. and J.O.J. declare they have no conflicts of interest. C.Z. has been a paid speaker for AbbVie, Eli Lilly, Novartis, CSL and LEO Pharma; has been a consultant for or served on advisory boards with AbbVie, Janssen‐Cilag, Novartis, Eli Lilly, Almirall and CSL; and has served as an investigator for AbbVie, Janssen‐Cilag, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Novartis, Regeneron, Takeda and LEO Pharma. L.S. has been a paid speaker for AbbVie, Eli Lilly, Novartis and LEO Pharma; has been a consultant for or served on advisory boards with AbbVie, Janssen‐Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall and Sanofi; has served as an investigator for AbbVie, Janssen‐Cilag, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Novartis, Regeneron and LEO Pharma; and has received research and educational grants from Novartis, Sanofi, Janssen‐Cilag and LEO Pharma.