Dental and Periodontal Health in Acute Intermittent Porphyria

Elin Storjord, Stella Airila-Månsson, Katarzyna Karlsen, Martin Madsen, Jim André Dahl, Anne Landsem, Hilde Fure, Judith Krey Ludviksen, Johannes Østrem Fjøse, Amy K Dickey, Bård Ove Karlsen, Erik Waage Nielsen, Tom Eirik Mollnes, Ole-Lars Brekke, Elin Storjord, Stella Airila-Månsson, Katarzyna Karlsen, Martin Madsen, Jim André Dahl, Anne Landsem, Hilde Fure, Judith Krey Ludviksen, Johannes Østrem Fjøse, Amy K Dickey, Bård Ove Karlsen, Erik Waage Nielsen, Tom Eirik Mollnes, Ole-Lars Brekke

Abstract

In the inherited metabolic disorder acute intermittent porphyria (AIP), high sugar intake prevents porphyric attacks due to the glucose effect and the following high insulin levels that may lower AIP disease activity. Insulin resistance is a known risk factor for periodontitis and sugar changes diabetogenic hormones and affects dental health. We hypothesized differences in homeostasis model assessment (HOMA) scores for insulin resistance in AIP cases vs. controls and in those with periodontitis. Our aim was to systematically study dental health in AIP as poor dental health was previously only described in case reports. Further, we aimed to examine if poor dental health and kidney failure might worsen AIP as chronic inflammation and kidney failure might increase disease activity. In 47 AIP cases and 47 matched controls, X-rays and physical examination of clinical attachment loss (CAL), probing pocket depth (PPD), and decayed missing filled teeth (DMFT) were performed. Dietary intake was evaluated through a diet logbook. Plasma cytokines and diabetogenic hormones were measured using multiplex technology and urine porphobilinogen and kidney and liver function by routine methods. An excel spreadsheet from the University of Oxford was used to estimate HOMA scores; beta cell function, HOMA%B (%B), insulin sensitivity, HOMA%S (%S), and insulin resistance HOMA-IR (IR), based on glucose and plasma (P) C-peptide. The Wilcoxon matched-pairs signed rank test, the Mann−Whitney U-test, and Spearman’s non-parametric correlation were used. Insulin (p = 0.007) and C-peptide (p = 0.006) were higher in the AIP cases with periodontitis versus those without. In AIP patients, the liver fibrosis index 4 correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.006); the estimated glomerular filtration rate correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.02). CAL ≥4 mm was correlated with chemokine ligand 11 and interleukin (IL)-13 (p = 0.04 for both), and PPD >5 mm was correlated with plasminogen activator inhibitor-1 (p = 0.003) and complement component 3 (p = 0.02). In conclusion, dental health in AIP cases was correlated with insulin resistance, inflammatory markers, and biomarkers of kidney and liver function, demonstrating that organ damage in the kidney and liver are associated with poorer dental health.

Keywords: cytokines; delta aminolevulinic acid; immunity; inflammation; innate immunity; periodontal disease; periodontitis; porphobilinogen; systemic health.

Conflict of interest statement

Amy Dickey reports receiving honoraria from Alnylam Pharmaceuticals for speaking engagements and porphyria-related consulting, and reports consulting honorarium from Recordati. No other potential conflict of interests were reported by the authors.

Figures

Figure 1
Figure 1
Possible pathways between acute intermittent porphyria (AIP) and dental health. Bård Ove Karlsen created Figure 1 in Adobe Illustrator version CC 2019 (23.0.0), Available online: https://www.adobe.com/products/illustrator.html (accessed on 10–27 June 2019).

References

    1. Strand L.J., Felsher B.F., Redeker A.G., Marver H.S. Heme biosynthesis in intermittent acute prophyria: Decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity. Proc. Natl. Acad. Sci. USA. 1970;67:1315–1320. doi: 10.1073/pnas.67.3.1315.
    1. Puy H., Gouya L., Deybach J.C. Porphyrias. Lancet. 2010;375:924–937. doi: 10.1016/S0140-6736(09)61925-5.
    1. Bissell D.M., Anderson K.E., Bonkovsky H.L. Porphyria. N. Engl. J. Med. 2017;377:862–872. doi: 10.1056/NEJMra1608634.
    1. Floderus Y., Shoolingin-Jordan P.M., Harper P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin. Genet. 2002;62:288–297. doi: 10.1034/j.1399-0004.2002.620406.x.
    1. Pischik E., Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl. Clin. Genet. 2015;8:201–214. doi: 10.2147/TACG.S48605.
    1. Sardh E., Harper P. RNAi therapy with givosiran significantly reduces attack rates in acute intermittent porphyria. J. Intern. Med. 2022;291:593–610. doi: 10.1111/joim.13443.
    1. Pallet N., Karras A., Thervet E., Gouya L., Karim Z., Puy H. Porphyria and kidney diseases. Clin. Kidney J. 2018;11:191–197. doi: 10.1093/ckj/sfx146.
    1. Handschin C., Lin J., Rhee J., Peyer A.K., Chin S., Wu P.H., Meyer U.A., Spiegelman B.M. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell. 2005;122:505–515. doi: 10.1016/j.cell.2005.06.040.
    1. Oliveri L.M., Davio C., Batlle A.M., Gerez E.N. ALAS1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice. Biochem. J. 2012;442:303–310. doi: 10.1042/BJ20111005.
    1. Di Pierro E., Granata F. Nutrients and Porphyria: An Intriguing Crosstalk. Int. J. Mol. Sci. 2020;21:3462. doi: 10.3390/ijms21103462.
    1. Storjord E., Dahl J.A., Landsem A., Fure H., Ludviksen J.K., Goldbeck-Wood S., Karlsen B.O., Berg K.S., Mollnes T.E., Nielsen E.W., et al. Systemic inflammation in acute intermittent porphyria: A case-control study. Clin. Exp. Immunol. 2017;187:466–479. doi: 10.1111/cei.12899.
    1. Iwasa F., Sassa S., Kappas A. The effects of acute-phase inducers and dimethyl sulphoxide on delta-aminolaevulinate synthase activity in human HepG2 hepatoma cells. Biochem. J. 1989;259:605–607. doi: 10.1042/bj2590605.
    1. Wang B., Rudnick S., Cengia B., Bonkovsky H.L. Acute Hepatic Porphyrias: Review and Recent Progress. Hepatol. Commun. 2019;3:193–206. doi: 10.1002/hep4.1297.
    1. Mastellos D.C., Ricklin D., Hajishengallis E., Hajishengallis G., Lambris J.D. Complement therapeutics in inflammatory diseases: Promising drug candidates for C3-targeted intervention. Mol. Oral Microbiol. 2016;31:3–17. doi: 10.1111/omi.12129.
    1. Ricklin D., Mastellos D.C., Reis E.S., Lambris J.D. The renaissance of complement therapeutics. Nat. Rev. Nephrol. 2018;14:26–47. doi: 10.1038/nrneph.2017.156.
    1. Sanz M., Ceriello A., Buysschaert M., Chapple I., Demmer R.T., Graziani F., Herrera D., Jepsen S., Lione L., Madianos P., et al. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J. Clin. Periodontol. 2018;45:138–149. doi: 10.1111/jcpe.12808.
    1. Brown R.S., Hays G.L., Jeansonne M.J., Lusk S.S. The management of a dental abscess in a patient with acute intermittent porphyria. A case report. Oral Surg. Oral Med. Oral Pathol. 1992;73:575–578. doi: 10.1016/0030-4220(92)90101-U.
    1. McGovern E., Fleming P., O’Marcaigh A. The dental management of five paediatric patients with a history of acute intermittent porphyria. Eur. Arch. Paediatr. Dent. Off. J. Eur. Acad. Paediatr. Dent. 2007;8:215–218. doi: 10.1007/BF03262600.
    1. Witbeck E. Acute intermittent porphyria: Clinical management and report of case. Spec. Care Dent. 1985;5:27–29. doi: 10.1111/j.1754-4505.1985.tb00930.x.
    1. Moore A.W., 3rd, Coke J.M. Acute porphyric disorders. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2000;90:257–262. doi: 10.1067/moe.2000.107976.
    1. Andersson C., Thunell S., Floderus Y., Forsell C., Lundin G., Anvret M., Lannfelt L., Wetterberg L., Lithner F. Diagnosis of acute intermittent porphyria in northern Sweden: An evaluation of mutation analysis and biochemical methods. J. Intern. Med. 1995;237:301–308. doi: 10.1111/j.1365-2796.1995.tb01179.x.
    1. Von Elm E., Altman D.G., Egger M., Pocock S.J., Gotzsche P.C., Vandenbroucke J.P., Initiative S. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. Lancet. 2007;370:1453–1457. doi: 10.1016/S0140-6736(07)61602-X.
    1. Savage A., Eaton K.A., Moles D.R., Needleman I. A systematic review of definitions of periodontitis and methods that have been used to identify this disease. J. Clin. Periodontol. 2009;36:458–467. doi: 10.1111/j.1600-051X.2009.01408.x.
    1. Papapanou P.N., Sanz M., Buduneli N., Dietrich T., Feres M., Fine D.H., Flemmig T.F., Garcia R., Giannobile W.V., Graziani F., et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Clin. Periodontol. 2018;45((Suppl. S20)):S162–S170. doi: 10.1111/jcpe.12946.
    1. Bergseth G., Ludviksen J.K., Kirschfink M., Giclas P.C., Nilsson B., Mollnes T.E. An international serum standard for application in assays to detect human complement activation products. Mol. Immunol. 2013;56:232–239. doi: 10.1016/j.molimm.2013.05.221.
    1. Van Vuuren B.J., Bergseth G., Mollnes T.E., Shaw A.M. Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement cascade activation in vitro using an activated complement serum calibration standard. J. Immunol. Methods. 2014;402:50–56. doi: 10.1016/j.jim.2013.11.010.
    1. Storjord E., Brekke O.L., Nielsen E.W. Safe usage of isotretinoin in a woman with latent acute intermittent porphyria. Acta Derm.-Venereol. 2007;87:267–268. doi: 10.2340/00015555-0178.
    1. Levey A.S., Stevens L.A., Schmid C.H., Zhang Y.L., Castro A.F., 3rd, Feldman H.I., Kusek J.W., Eggers P., Van Lente F., Greene T., et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009;150:604–612. doi: 10.7326/0003-4819-150-9-200905050-00006.
    1. Storjord E., Dahl J.A., Landsem A., Ludviksen J.K., Karlsen M.B., Karlsen B.O., Brekke O.L. Lifestyle factors including diet and biochemical biomarkers in acute intermittent porphyria: Results from a case-control study in northern Norway. Mol. Genet Metab. 2018;128:254–270. doi: 10.1016/j.ymgme.2018.12.006.
    1. Chen G.Y., Nunez G. Sterile inflammation: Sensing and reacting to damage. Nat. Rev. Immunol. 2010;10:826–837. doi: 10.1038/nri2873.
    1. Robinson M.W., Harmon C., O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell. Mol. Immunol. 2016;13:267–276. doi: 10.1038/cmi.2016.3.
    1. Janket S.J., Javaheri H., Ackerson L.K., Ayilavarapu S., Meurman J.H. Oral Infections, Metabolic Inflammation, Genetics, and Cardiometabolic Diseases. J. Dent. Res. 2015;94:119S–127S. doi: 10.1177/0022034515580795.
    1. Yu Y.H., Chasman D.I., Buring J.E., Rose L., Ridker P.M. Cardiovascular risks associated with incident and prevalent periodontal disease. J. Clin. Periodontol. 2015;42:21–28. doi: 10.1111/jcpe.12335.
    1. Bergstrom J. Smoking rate and periodontal disease prevalence: 40-year trends in Sweden 1970–2010. J. Clin. Periodontol. 2014;41:952–957. doi: 10.1111/jcpe.12293.
    1. Bostrom E.A., Kindstedt E., Sulniute R., Palmqvist P., Majster M., Holm C.K., Zwicker S., Clark R., Onell S., Johansson I., et al. Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines. PLoS ONE. 2015;10:e0134608. doi: 10.1371/journal.pone.0134608.
    1. Aarsand A.K., Petersen P.H., Sandberg S. Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria. Clin. Chem. 2006;52:650–656. doi: 10.1373/clinchem.2005.060772.
    1. Unzu C., Sampedro A., Sardh E., Mauleon I., Enriquez de Salamanca R., Prieto J., Salido E., Harper P., Fontanellas A. Renal failure affects the enzymatic activities of the three first steps in hepatic heme biosynthesis in the acute intermittent porphyria mouse. PLoS ONE. 2012;7:e32978. doi: 10.1371/journal.pone.0032978.
    1. Zhao D., Khawaja A.T., Jin L., Li K.Y., Tonetti M., Pelekos G. The directional and non-directional associations of periodontitis with chronic kidney disease: A systematic review and meta-analysis of observational studies. J. Periodontal Res. 2018;53:682–704. doi: 10.1111/jre.12565.
    1. Uwitonze A.M., Murererehe J., Ineza M.C., Harelimana E.I., Nsabimana U., Uwambaye P., Gatarayiha A., Haq A., Razzaque M.S. Effects of vitamin D status on oral health. J. Steroid Biochem. Mol. Biol. 2018;175:190–194. doi: 10.1016/j.jsbmb.2017.01.020.
    1. Antonoglou G.N., Knuuttila M., Niemela O., Raunio T., Karttunen R., Vainio O., Hedberg P., Ylostalo P., Tervonen T. Low serum level of 1,25(OH)2 D is associated with chronic periodontitis. J. Periodontal Res. 2015;50:274–280. doi: 10.1111/jre.12207.
    1. Yamamoto E., Jorgensen T.N. Immunological effects of vitamin D and their relations to autoimmunity. J. Autoimmun. 2019;100:7–16. doi: 10.1016/j.jaut.2019.03.002.
    1. Nagao Y., Kawahigashi Y., Sata M. Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection. Hepat. Mon. 2014;14:e23264. doi: 10.5812/hepatmon.23264.
    1. Panezai J., Ghaffar A., Altamash M., Sundqvist K.G., Engstrom P.E., Larsson A. Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters. PLoS ONE. 2017;12:e0188945. doi: 10.1371/journal.pone.0188945.
    1. Ebersole J.L., Dawson D., 3rd, Emecen-Huja P., Nagarajan R., Howard K., Grady M.E., Thompson K., Peyyala R., Al-Attar A., Lethbridge K., et al. The periodontal war: Microbes and immunity. Periodontology 2000. 2017;75:52–115. doi: 10.1111/prd.12222.
    1. Lee C.C., Lorenzo C., Haffner S.M., Wagenknecht L.E., Festa A., Goodarzi M.O., Stefanovski D., Olson N.C., Norris J.M., Rewers M.J., et al. The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: The Insulin Resistance Atherosclerosis Study (IRAS) Diabetologia. 2013;56:112–120. doi: 10.1007/s00125-012-2741-8.
    1. Abranches M.V., Oliveira F.C., Conceicao L.L., Peluzio M.D. Obesity and diabetes: The link between adipose tissue dysfunction and glucose homeostasis. Nutr. Res. Rev. 2015;28:121–132. doi: 10.1017/S0954422415000098.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi