Abstract
This cross-sectional study of 125 residents of 7 nursing homes in the Netherlands evaluates the prevalence of pemphigoid as a potentially unrecognized cause of pruritus.
Bullous pemphigoid may commonly present as pruritus in elderly patients.1 Approximately 1 in 5 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 disease.3,4 Our aim was to assess the prevalence of pemphigoid in a high-risk population of nursing home residents, with nonbullous pemphigoid as a potentially unrecognized cause of pruritus.
Methods
This prospective cross-sectional study was conducted in 7 nursing homes affiliated with the University Network for Elderly Care of the University Medical Center Groningen in the Netherlands between July 2016 and December 2017. Participants 65 years or older were eligible when a routine venipuncture was scheduled and 1 extra blood sample could be withdrawn. Exclusion criteria were systemic immunosuppressive therapy or life expectancy of less than 4 weeks. Written informed consent was required of cognitively capable participants or legal representatives of cognitively impaired participants, and the study was approved by the University Medical Center Groningen institutional review board.
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 was only performed on a voluntary basis owing to ethical considerations.
Results
We enrolled 125 nursing home residents (mean [SD] age, 84.1 [6.9] years); 75% had a history of neurodegenerative disease (n = 94). Pruritus was present in 59 of 125 participants (47%) and of chronic duration (>6 weeks) in 48 participants (81%). Pemphigoid was diagnosed in 7 of 125 participants, yielding an overall prevalence of 6% (Table). Three participants with bullous pemphigoid had already been diagnosed. Nonbullous pemphigoid was unrecognized and newly diagnosed in 4 participants, all of whom had a history of chronic pruritus. Nonbullous skin manifestations consisted of erythematous papules and/or nodules, urticarial plaques, and excoriations, mainly distributed on the back and extremities. Nonspecific serological findings in study participants without pemphigoid diagnosis were single detection of IgA by IIF SSS (2 cases), and low titers of IgG autoantibodies by BP180 NC16A (10 cases) or BP230 enzyme-linked immunosorbent assay (3 cases).
Table. Characteristics of the 7 Study Patients Diagnosed With Pemphigoid.
| Pemphigoid Phenotype | Clinical Findings | IIF SSS (Roof Staining) | IIF ME | Antigen by ELISA BP180, NC16A, BP230, Immunoblot | DIF Anti-BMZa | Treatment and Follow-up (Duration) |
|---|---|---|---|---|---|---|
| Bullous | Mild pruritus, moderate blisters, erythema, excoriations and hyperpigmentation on abdomen, back and extremities | IgG3+ | IgG+ | BP180, BP230 | NA | Lesional superpotent corticosteroids |
| Partial remission (9 mo), until death due to natural causes | ||||||
| Bullous | Severe pruritus, generalized blisters, erosions, erythema, papules and urticaria | IgG3+ | IgG+/– | BP180 | IgG, C3c | Oral corticosteroids, doxycycline, lesional super potent corticosteroids |
| IgA1+ | Linear | Death due to natural causes shortly after study examination | ||||
| Bullous | Mild pruritus, localized blisters on legs with excoriations, hyperpigmentation and hematoma | IgG1+ | IgG+ | BP180, BP230 | IgG, C3c | Oral corticosteroids, methotrexate (15 mg/wk) and lesional superpotent corticosteroids |
| N-serrated | Complete remission (18 mo) | |||||
| Nonbullous | Severe generalized pruritus with excoriations, papules, erythema | IgG1+ | IgG+ | BP230 | IgA | Doxycycline, whole-body superpotent corticosteroids |
| N-serrated | Partial remission (17 mo) | |||||
| Nonbullous | Severe pruritus with excoriations, erythema, papules and urticaria on back and extremities | IgG3+ | IgG+ | BP230 | Negative | Methotrexate (7.5 mg/wk) |
| Complete remission (11 mo), flare after tapering and complete remission (9 mo) after retreatment | ||||||
| Nonbullous | Severe pruritus with excoriations, erythema and urticaria on back and extremities | IgG1+ | IgG+ | BP230 | Negative | Methotrexate (7.5 mg/wk) |
| Complete remission (7 mo), flare after tapering and complete remission (1 mo) after retreatment, until death due to natural causes. | ||||||
| Nonbullous | Mild pruritus with erythema, papules and excoriations on extremities | IgG2+ | IgG+ | BP230 | Negative | Topical steroid ointments |
| Complete remission (18 mo) |
Abbreviations: BMZ, basement membrane zone; C3c, complement C3; DIF, direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G; IgA, immunoglobulin A; IIF, indirect immunofluorescence; ME, monkey esophagus; NA, not available; NC16A, noncollagenous 16A domain of BP180; SSS, salt-split skin; +, positive; +/−, doubtful positive.
Not a study requirement, performed on a voluntary basis.
Discussion
We observed a prevalence of pemphigoid of 6% among nursing home residents. More than half of these patients did not show blisters and had not yet been diagnosed with pemphigoid. Only 2 previous studies to our knowledge have assessed bullous pemphigoid in nursing home residents, and these reported a prevalence of 1% by survey5 and an annual incidence of 5% by skin biopsy.6
The present study confirms that the prevalence of pemphigoid is substantially higher in nursing home residents than in the general population, which has been estimated at 0.026% in total and 0.3% in persons 85 years or older (unpublished 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 direct immunofluorescence is required to exclude pemphigoid in cases with negative IIF SSS.2
The finding of this study that nonbullous pemphigoid was more frequent than bullous pemphigoid merits attention from clinicians. We therefore recommend including pemphigoid in the diagnostic workup of chronic pruritus in elderly patients.
References
- 1.Lamberts A, Meijer JM, Pas HH, Diercks GFH, Horváth B, Jonkman MF. 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 [DOI] [PubMed] [Google Scholar]
- 2.Meijer JM, Diercks GFH, de Lang EWG, Pas HH, Jonkman MF. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Hübner F, Recke A, Zillikens D, Linder R, Schmidt E. Prevalence and age distribution of pemphigus and pemphigoid diseases in Germany. J Invest Dermatol. 2016;136(12):2495-2498. doi: 10.1016/j.jid.2016.07.013 [DOI] [PubMed] [Google Scholar]
- 4.Försti A-K, 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. doi: 10.1038/srep37125 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Tseng H-W, Lam H-C, Ger L-P, Liang CK, Liou HH, Wu CS. A survey of dermatological diseases among older male adults of a Veterans Home in Southern Taiwan. Aging Clin Exp Res. 2015;27(2):227-233. doi: 10.1007/s40520-014-0260-9 [DOI] [PubMed] [Google Scholar]
- 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(8):1405-1406. doi: 10.1111/j.1532-5415.2004.52379_5.x [DOI] [PubMed] [Google Scholar]