Increased Risk of Stroke in Patients With Bullous Pemphigoid

Yang, Ya‐Wen; Chen, Yi Hua; Xirasagar, Sudha; Lin, Herng Ching

doi:10.1161/strokeaha.110.596361

Cited by 65 publications

(74 citation statements)

References 49 publications

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“…The previous studies, except the ones considering motor neuron diseases 8 and strokes 15 , have most probably missed this connection because of small study populations or short follow-up time. Still, the 2-fold increased risk of viral meningitis or viral encephalitis following a diagnosis of BP was unexpected.…”

Section: Discussionmentioning

confidence: 99%

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

Försti

Jokelainen

Ansakorpi

et al. 2016

Journal of Investigative Dermatology

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Bullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9-8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0-3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP.Bullous pemphigoid (BP) is an autoimmune skin disease with incidence varying between 0.25 and 4.28/100.000 per year 1-3 . The age-adjusted incidence of BP has been reported to be on the rise 1-3 . BP typically presents with severe itching and blistering of the skin, but in up to 20% of patients blisters are completely absent and only excoriations or eczematous, urticated lesions are observed 4 . BP typically affects elderly people, has many comorbidities and carries an elevated risk of death compared with the general population of the same age [1][2][3][4] . The pathogenesis of BP is characterized by autoantibodies directed against the hemidesmosomal components between the basal keratinocytes of the epidermis and the extracellular matrix of the dermis, resulting in subepidermal blister formation. The main autoantigen is bullous pemphigoid antigen 180 (BP180, also known as BPAG 2 or collagen XVII), though BP patients may also have autoantibodies against bullous pemphigoid antigen 230 (BP230 or BPAG1), another hemidesmosomal protein 4 . Several studies have established an association between BP and neurological disorders, especially stroke, dementia and Parkinson's disease [5][6][7][8] . The mechanism behind this association has been suggested to be an autoinflammatory reaction against BP180 or the neuronal isoform of BP230 in the human brain 9,10 . However, previous studies did not specify the types of dementia or cerebrovascular stroke. Neurological disorders precede BP 5,6 , but it is unclear, whether the risk of developing neurological disorders is elevated after a diagnosis of BP.

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Section: Discussionmentioning

confidence: 99%

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

Försti

Jokelainen

Ansakorpi

et al. 2016

Journal of Investigative Dermatology

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“…Recently, one study suggested that cardiovascular events and thromboembolic diseases are important causes of death in patients with BP; the risk of stroke after a diagnosis of BP (relative to the general population) was investigated in Taiwan. The study sample included 390 patients with BP, versus 1950 matched subjects in a comparison group [14]. Other authors have also reported statistically significant cardiovascular and neurologic alterations between patients affected by BP and matched control groups [14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

“…The study sample included 390 patients with BP, versus 1950 matched subjects in a comparison group [14]. Other authors have also reported statistically significant cardiovascular and neurologic alterations between patients affected by BP and matched control groups [14][15][16][17][18]. As we have previously noted, most classic skin immunofluorescence studies have been performed with monofluorochome techniques, frequently utilizing FITC.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and antigen presenting cells, and non-basement membrane zone pathology in a case of bullous pemphigoid

Velez¹,

Brown²,

Howard³

2012

Our Dermatol Online

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Background: When performing direct and indirect skin immunofluorescence (DIF, IIF) in bullous pemphigoid (BP) utilizing single fluorophores such as fluorescein isothiocyanate (FITC), the presence of "background" fluorescence is commonly described. Aim of reporting this case: Our laboratory has noted that what is termed "background" could represent a complex immune response in BP, that may be present in addition to the classical deposits of immunoglobulins and/or complement at the dermal/epidermal basement membrane zone (BMZ). Therefore, we simultaneously used multiple colored fluorophores to further investigate this possibility. Case Report: A 68-year-old male was evaluated for the presence of rapidly appearing vesicles and bullae on the chest, with additional pruritus. Methods: Skin biopsies for hematoxylin and eosin (H&E) staining, as well as for DIF, IIF, salt split skin and immunohistochemistry (IHC) analyses were performed. Results: H&E staining demonstrated a subepidermal blistering disorder. Within the dermis, a mild, superficial and deep, perivascular infiltrate of lymphocytes, histiocytes and eosinophils was observed. A few infiltrate cells displayed positive DIF staining for CD5, CD8 and CD45 around dermal blood vessels, nerves and eccrine sweat glands. In contradistinction, CD4, CD56 and Granzyme B staining was predominantly negative in these areas. DIF, IIF and salt split skin studies revealed a strong presence of IgG, Complement/C3, IgM and fibrinogen in linear patterns at the BMZ. Around the upper dermal perivascular infiltrate, HAM56 and CD68 positive cells were also noted. Positive DIF staining for CD1a was found suprajacent to the blister in the epidermis. Utilizing identical antibodies, we repeated our staining with the IHC technique, to address the issue of autofluorescence in DIF staining. Our IHC findings correlated with DIF and IIF results. Conclusion: Using multiple DIF fluorophores in this case of BP, we observed autoantibodies to structures such dermal nerves, blood vessels and eccrine sweat glands, that were not appreciated using FITCI alone. We propose the use of this technique in autoimmune skin diseases. In addition, we observed a prominent T cytotoxic cell infiltrate, that warrants further characterization. Streszczenie Wstęp: Podczas wykonywania bezpośredniej i pośredniej immunofluorescencji skóry (DIF, IIF) w pemfigoidzie (BP) wykorzystuje się pojedyncze fluorofory takie jak izotiocyjanian fluoresceiny (FITC), a obecność "tła" fluorescencji jest powszechnie opisane. Cel niniejszego raportu: Nasze laboratorium zanotowało, że to, co jest określane jako "tło" może stanowić kompleksową odpowiedź immunologiczną w BP, która może być obecna dodatkowo w postaci klasycznych depozytów immunoglobulin i/lub dopełniacza w skórze/naskórku strefie błony podstawnej (BMZ). Dlatego równoczesne stosowaliśmy wiele kolorów fluoroforów do dalszego zbadania tej możliwości. Opis przypadku: 68-letni mężczyzna był oceniany pod kątem obecności szybko pojawiających się pęcherzyków i pęcherzy na piers...

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“…The association between these dermatoses and AIS may be causal and possibly explained by intrinsic inflammatory physiopathological abnormalities leading to thrombosis and hypercoagulability [3,4,5,6,7]. However, whether the overrepresentation of traditional risk factors may be a potential contributor for the higher incidence of AIS observed in some cohorts of patients with dermatoses is currently unknown [7,8,9,10,11,12,13,14,15]. …”

Section: Introductionmentioning

confidence: 99%

“…There is limited data on the epidemiology and prevalence of risk factors within these dermatoses in AIS populations, aside from the information derived from studies based on outpatient populations [3,7,8,15,16]. To this end, the primary objective of this study was to assess the prevalence of systemic diseases associated with dermatoses in admissions of AIS patients in the USA, with specific examination of traditional risk factors.…”

Section: Introductionmentioning

confidence: 99%

The Prevalence of Systemic Diseases Associated with Dermatoses and Stroke in the United States: A Cross-Sectional Study

Kupetsky

Rincón²

2013

Dermatology

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Aims: To evaluate the prevalence of systemic diseases associated with dermatoses and conventional risk factors in patients with acute ischemic stroke (AIS). We hypothesized that conventional risk factors would not be overrepresented in AIS admissions of patients with dermatoses. Methods: Cross-sectional study. We ascertained admissions of AIS with and without the following: systemic lupus erythematosus (SLE), psoriasis (PSO), scleroderma (SSc), dermatomyositis (D-MS), bullous pemphigoid (BP), and Behçet's disease. Results: 6,454,877 admissions had a primary diagnosis of AIS of whom 34,345 had dermatoses. The prevalence of dermatoses within AIS was 0.5% (95% CI 0.32-0.55). Prevalent dermatoses at the time of AIS admission were SLE (63%), PSO (18%), SSc (12%), D-MS (4%), and BP (2%). There were no significant differences in the prevalence of traditional risk factors among dermatoses; however, these patients tended to be younger women. Hospital days of care (median 4, IQR 3-8, vs. 5, IQR 3-9, p = 0.005) and in-hospital mortality were lower (5 vs.7%, p = 0.05) for those admissions of AIS patients with dermatoses. Conclusions: The prevalence of systemic diseases associated with dermatoses is rare in admissions of patients with AIS. Traditional risk factors were not overrepresented in AIS admissions with dermatoses. In-hospital mortality and length of stay were significantly lower in admissions of patients with AIS and dermatoses.

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Increased Risk of Stroke in Patients With Bullous Pemphigoid

Cited by 65 publications

References 49 publications

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

Cytotoxic and antigen presenting cells, and non-basement membrane zone pathology in a case of bullous pemphigoid

The Prevalence of Systemic Diseases Associated with Dermatoses and Stroke in the United States: A Cross-Sectional Study

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