University of Groningen
Pemphigoid diseases: Insights in the nonbullous variant and disease management
Lamberts, Aniek
DOI:
10.33612/diss.132159641
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Publication date: 2020
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Lamberts, A. (2020). Pemphigoid diseases: Insights in the nonbullous variant and disease management. University of Groningen. https://doi.org/10.33612/diss.132159641
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CHAPTER 5
Prevalence of pemphigoid as a potentially unrecognized
cause of pruritus in nursing home residents
Aniek Lamberts*
1, Joost M. Meijer*
1, Hendrika J. Luijendijk
2, Gilles F.H.
Diercks
1, Hendri H. Pas
1, Sytse U. Zuidema
2, Marcel F. Jonkman
1†* Authors contributed equally.
1 University of Groningen, University Medical Center Groningen, Department of
Dermatology, Center for Blistering Diseases, Groningen, The Netherlands
2 University of Groningen, University Medical Center Groningen, Department of
General Practice and Elderly Care Medicine, Groningen, The Netherlands
Published in the Journal of the American Medical Association Dermatology. 2019 Nov 6. doi: 10.1001/jamadermatol.2019.3308. [Epub ahead of print]
Bullous pemphigoid may commonly present as pruritus in elderly patients.1
Approximately one in five patients with pemphigoid has nonbullous skin manifestations that resemble other pruritic skin diseases, termed nonbullous pemphigoid.1,2 According to recently established minimal diagnostic criteria the
diagnosis of bullous and nonbullous pemphigoid can be based on either a skin biopsy, or a serum sample.2 The prevalence of bullous pemphigoid strongly
increases with age and the disease is associated with neurodegenerative diseases, such as dementia and Parkinson’s disease.3,4 Our aim was to assess the prevalence
of pemphigoid in a high-risk population of nursing home residents, with nonbullous pemphigoid a potential unrecognized cause of pruritus.
Methods
This prospective cross-sectional study was conducted in seven nursing homes affiliated with the University Network for Elderly Care of the UMCG in the
Netherlands between July 2016 and December 2017. Participants aged 65 years or older were eligible when a routine vena punction was scheduled and one extra blood sample could be withdrawn. Exclusion criteria were systemic
immunosuppressive therapy or life expectancy of less than four weeks. Written informed consent was required of cognitively capable participants, or legal representatives of cognitively impaired participants.
Pruritus was assessed by skin examination using the Bullous Pemphigoid Disease Area Index (BPDAI) excoriation score. Cognitively competent participants rated pruritus from 0 to 10, and for cognitively incompetent participants nursing staff was interviewed about signs of pruritus. Diagnostic criteria for pemphigoid were: 1) pruritus and/or skin blisters, and 2) positive epidermal side staining of IgG by indirect immunofluorescence on salt-split skin (IIF SSS).2 A skin biopsy for direct
immunofluorescence (DIF) was only performed on voluntary basis due to ethical considerations.
Results
We enrolled 125 nursing home residents (figure 1) on average 84.1 years [SD 6.9], with a history of neurodegenerative disease in 75%. Pruritus was present in 59 of 125 participants (47%) and of chronic duration (>6 weeks) in 48 participants (81%). Pemphigoid was diagnosed in seven of 125 participants, yielding an overall
participants with bullous pemphigoid had already been diagnosed. Nonbullous pemphigoid was unrecognized and newly diagnosed in four participants, all of whom had a history of chronic pruritus. Nonbullous skin manifestations consisted of erythematous papules/nodules, urticarial plaques and excoriations, mainly distributed on the back and extremities (figure 2). Non-specific serological findings in controls were single detection of IgA by IIF SSS (two cases), and low titers of IgG autoantibodies by BP180 NC16A (ten cases) or BP230 ELISA (three cases).
Discussion
We observed a prevalence of pemphigoid of 6% among nursing home residents. More than half of the cases did not show blisters and had not yet been diagnosed with pemphigoid.
Only two previous studies assessed bullous pemphigoid in nursing home residents, and reported a prevalence of 1% by survey5, and an annual incidence of 5% by skin
biopsy.6
Our study confirms that the prevalence of pemphigoid is substantially higher in nursing home residents than in the general population, which was estimated at 0.026% in total and 0.3% in persons aged ≥85 years (data provided by the
authors).3 Possibly this finding might be explained by neurodegenerative diseases
preceding development of pemphigoid as a result of cross-reactivity between neuronal and epithelial isoforms of the pemphigoid antigens.4 While the
confirmative IIF SSS test is highly specific, the sensitivity is approximately 80% and a skin biopsy for DIF required to exclude pemphigoid in negative cases.2
The striking finding of this study that nonbullous pemphigoid was more frequent than bullous pemphigoid merits attention from clinicians. We therefore recommend to include pemphigoid in the diagnostic work-up of chronic pruritus in elderly patients.
References
1 Lamberts A, Meijer JM, Diercks GFH, et al. Nonbullous pemphigoid: Insights in clinical and diagnostic findings, treatment responses, and prognosis. J Am Acad Dermatol 2019; 81(2):355-363. doi:10.1016/j.jaad.2019.04.029
2 Meijer JM, Diercks GFH, de Lang EWG, et al. Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid. JAMA Dermatol. 2019;155(2):158-165 doi:10.1001/jamadermatol.2018.4390.
3 Hubner F, Recke A, Zillikens D, et al. Prevalence and Age Distribution of Pemphigus and Pemphigoid Diseases in Germany. J. Invest. Dermatol. 2016; 136:2495–8.
4 Forsti AK, Jokelainen J, Ansakorpi H, et al. Psychiatric and neurological disorders are associated with bullous pemphigoid - a nationwide Finnish Care Register study. Sci Rep 2016; 6:37125. 5 Tseng HW, Lam HC, Ger LP, et al. A survey of dermatological diseases among older male adults
of a Veterans Home in Southern Taiwan. Aging Clin Exp Res 2015; 27:227–33.
6 Fernandez-Viadero C, Arce Mateos F, Verduga Velez R, Crespo Santiago D. Blisters in a nursing home: bullous pemphigoid more often than we think? J. Am. Geriatr. Soc. 2004; 52:1405–6.
Figure 2. Clinical features of a 89 year old female nursing home resident with nonbullous pemphigoid. A) Excoriated erythematous papules and excoriations on the back.
B) Complete remission achieved after 6 weeks of treatment with methotrexate 7.5mg per week monotherapy. C) Excoriated papules and urticarial plaques on the right flank.
D) Excoriated erythematous papules and nodules on the left arm.
A B
ha ra ct er is tic s o f n ur si ng h om e r es id en ts d ia gn os ed w ith p em ph ig oi d id Cl ini ca l f indi ng s, sk in l es io ns a nd di st rib ut io n IIF SSS (r oo f st ai ni ng ) IIF ME Ant ig en by E LI SA BP 18 0 N C1 6A , BP 230, im m uno bl ot DI F* ant i-BM Z Tr ea tm ent a nd f ol lo w -up ( dur at io n) m ild p ru rit us , m od er at e b lis te rs , er yt hem a, ex cor ia tion s a nd h yp er -pi gm en ta tio n o n a bd om en , b ac k an d ex tr em iti es Ig G 3 + Ig G + BP 180, B P230 n.a . Les ion al s up er p ot en t c or tic os ter oi ds Pa rt ia l r em is si on (9 m on th s) , u nt il d ea th d ue to na tu ra l c au se s. sev er e p ru rit us , g en er al iz ed b lis te rs , er os ion s, er yt hem a, p ap ul es a nd ur tic ar ia Ig G 3 + Ig A 1 + Ig G +/ - BP 180 IgG , C3 c lin ea r Or al c or tic os ter oi ds , d ox yc yc lin e, les ion al s up er pot en t c or tic os ter oi ds D ea th d ue to n at ur al c au se s s ho rt ly a ft er s tu dy ex ami nat io n m ild p ru rit us , l oc al iz ed b lis te rs o n l eg s w ith ex cor ia tion s, h yp er -p ig m en ta tio n an d h emat oma Ig G 1 + Ig G + BP 180, B P230 IgG , C3 c n-ser ra ted Or al c or tic os ter oi ds , m et hot rex at e ( 15 m g/ w k) a nd les ion al s up er p ot en t c or tic os ter oi ds Com pl et e r em is si on ( 18 m on th s) us sev er e g en er al iz ed p ru rit us w ith ex cor ia tion s, p ap ul es , er yt hem a Ig G 1 + Ig G + BP 230 Ig A n-ser ra ted D ox yc yc lin e, w hol e-bod y s up er p ot en t cor tic os ter oi ds . Pa rt ia l r em is sion (1 7 m on th s) us sev er e p ru rit us w ith ex cor ia tion s, er yt he m a, p ap ul es a nd u rt ic ar ia o n ba ck a nd ex tr em iti es Ig G 3 + Ig G + BP 230 ne gat iv e Me th ot re xa te (7 .5 m g/ w k) le d t o com pl et e r em is si on (1 1 m on th s) , f la re a ft er ta pe rin g a nd c om pl et e r em is si on (9 m on th s) a ft er ret rea tm en t us sev er e p ru rit us w ith ex cor ia tion s, er yt he m a a nd u rt ic ar ia o n b ac k a nd ex tr em iti es Ig G 1 + Ig G + BP 230 ne gat iv e M et hot rex at e ( 7. 5m g/ w k) led to c om pl et e re m is si on (7 m on th s) , f la re a ft er ta pe rin g a nd com pl et e r em is si on (1 m on th ) a ft er ret rea tm en t, un til d ea th d ue to n at ur al c au se s. us m ild p ru rit us w ith e ry th em a, p ap ul es an d ex cor ia tion s on ex tr em iti es Ig G 2 + Ig G + BP 230 ne gat iv e To pi ca l s te ro id o in tm en ts Com pl et e r em is si on (1 8 m on th s) M , m al e; Ig G , i m m un og lo bu lin G ; I gA , i m m un og lo bu lin e A ; C 3c , c om pl em en t C 3; +, pos iti ve; -, n eg at iv e; +/ -, d ou bt fu l p os iti ve ; I IF , i nd ire ct lu or es ce nc e; S SS , s al t-sp lit s ki n; M E, m on key es op ha gu s; E LI SA , en zym e l in ked im m un os or ben t a ss ay; N C1 6A , n on -c ol la gen ou s 1 6A d om ai n of B P1 80 ; im m un of lu or es ce nc e; B M Z, b as em en t m em br an e z on e. * N o s tu dy re qu ire m en t, p er fo rm ed a t v ol un ta ry b as is
Acknowledgements
The authors wish to thank the participating care organisations and staff of the SSENIOR Study Group*, and Janny Zuiderveen, Gonnie Meijer, Marije van der Molen and Laura Nijen-Vos (Immunodermatology Laboratory, Department of Dermatology, University Medical Center Groningen, the Netherlands) for technical assistance and performing laboratory tests.
*SSENIOR Study Group:
University Medical Center Groningen: Alet Leus, Nanda Hommes Patyna Bloemkamp Bolsward: Erica Gerbrandy, Mariëlle Gaster Dignis De Omloop Norg, De Enk Zuidlaren: Carolien van Bruggen Interzorg Anholt Assen: Sifra van Rest, Arenda Krol
Dignis Blauwbörgje Groningen: Margreet Schaaf ZINN De Es/De Dilgt Haren: Arnold Bisschop
