Pemfigus – Rokowania, prognozy i postęp choroby

Pemfigus
Rokowania, prognozy i postęp choroby

Pemfigus, obejmujący pemfigus zwyczajny (PV) i liściasty (PF), to rzadkie autoimmunologiczne choroby pęcherzowe skóry i błon śluzowych, których rokowanie uległo poprawie dzięki terapii kortykosteroidami i lekami immunosupresyjnymi. Śmiertelność w PV obecnie wynosi około 5-15%, podczas gdy w nieleczonym PV przekracza 75%. Niezależne czynniki ryzyka całkowitej śmiertelności to wiek zachorowania ≥65 lat oraz współistniejąca choroba wieńcowa serca (HR=4,27; 95% CI: 1,5-12,13; p=0,006). Wysoki poziom autoprzeciwciał anty-Dsg1 (≥100 U/mL) w chwili diagnozy jest czynnikiem ryzyka w analizie jednoczynnikowej, jednak po korekcie względem wieku nie pozostaje istotny statystycznie. Główne przyczyny zgonów to zakażenia, zaburzenia wodno-elektrolitowe oraz powikłania terapii kortykosteroidowej. Pemfigus paraneoplastyczny (PNP) cechuje się wysoką śmiertelnością (75-90%), głównie z powodu niewydolności oddechowej, a rokowanie zależy od charakteru nowotworu i obecności zarostowego zapalenia oskrzelików.

pemfigusie”>Prognoza w Pemfigusie

Pemfigus jest grupą rzadkich, autoimmunologicznych chorób pęcherzowych dotykających skórę i błony śluzowe. Rokowanie w pemfigusie uległo znacznej poprawie na przestrzeni ostatnich dekad, głównie dzięki wprowadzeniu leczenia kortykosteroidami i lekami immunosupresyjnymi oszczędzającymi sterydy. Mimo to, określenie czynników wpływających na przeżycie pacjentów z pemfigusem stanowi istotny element opieki klinicznej.¹²

Wskaźniki śmiertelności w pemfigusie

Przed wprowadzeniem kortykosteroidów do terapii, pemfigus zwyczajny (pemphigus vulgaris, PV) był chorobą często prowadzącą do zgonu. Obecnie, dzięki odpowiedniemu leczeniu, śmiertelność uległa drastycznemu zmniejszeniu do około 5-15%. Jednak w przypadku nieleczonego pemfigusa zwyczajnego, śmiertelność nadal przekracza 75%. Pacjenci pozostawieni bez leczenia zazwyczaj umierają w ciągu pierwszych kilku lat od postawienia diagnozy.³⁴

Śmiertelność pacjentów z pemfigusem zwyczajnym jest trzykrotnie wyższa niż w populacji ogólnej. Większość zgonów następuje w pierwszych latach choroby, a jeśli pacjent przeżyje 5 lat, rokowanie jest dobre. Wczesne rozpoznanie i leczenie choroby prawdopodobnie ułatwia jej kontrolę w porównaniu z zaawansowanym stadium.⁵

Czynniki ryzyka wpływające na przeżycie

Badania retrospektywne wykazały szereg czynników ryzyka związanych z całkowitą śmiertelnością w pemfigusie zwyczajnym i liściastym (pemphigus foliaceus):⁶⁷

Wiek zachorowania ≥65 lat – jest niezależnym czynnikiem ryzyka związanym ze zwiększoną śmiertelnością całkowitą u pacjentów z pemfigusem zwyczajnym i liściastym⁸⁹
Choroby współistniejące – szczególnie choroby układu sercowo-naczyniowego:
- Choroba wieńcowa serca w momencie diagnozy (HR=4,27; 95% CI: 1,5-12,13; p=0,006)¹⁰
- Arytmia serca w momencie diagnozy (HR=6,19; 95% CI: 1,77-21,64; p=0,004)¹¹
Poziom autoprzeciwciał przeciw desmogleinie 1 (anty-Dsg1) ≥100 U/mL w momencie diagnozy¹²¹³

Analiza wieloczynnikowa zidentyfikowała wiek zachorowania ≥65 lat oraz obecność choroby wieńcowej serca w momencie diagnozy jako niezależne czynniki ryzyka związane z całkowitą śmiertelnością.¹⁴¹⁵

Chorobowo-specyficzne czynniki prognostyczne

Oprócz powszechnych czynników prognostycznych, takich jak starszy wiek i współistniejące choroby układu krążenia, poziom autoprzeciwciał zidentyfikowano jako specyficzny dla choroby czynnik związany z całkowitą śmiertelnością w pemfigusie zwyczajnym. Poziom przeciwciał anty-Dsg1 ≥100 U/mL w momencie diagnozy stanowił czynnik ryzyka zgonu u pacjentów z PV w początkowej analizie jednoczynnikowej, chociaż po skorygowaniu względem wieku jako zmiennej ciągłej lub dychotomicznej, zależność ta nie była istotna statystycznie (p≥0,05).¹⁶¹⁷¹⁸

Przyczyny zgonów w pemfigusie

Główne przyczyny zgonów w pemfigusie obejmują:¹⁹²⁰

Zakażenia bakteryjne i wirusowe
Zaburzenia równowagi wodno-elektrolitowej
Powikłania związane ze stosowaniem wysokich dawek kortykosteroidów

Szczególne podtypy pemfigusa i ich rokowanie

Pemfigus paraneoplastyczny

Pemfigus paraneoplastyczny (PNP) jest wyjątkową autoimmunologiczną chorobą pęcherzową, mogącą dotykać wielu narządów poza skórą. Jest to choroba zagrażająca życiu, związana z chorobą nowotworową, najczęściej pochodzenia limfoproliferacyjnego.²¹

Rokowanie w PNP jest zasadniczo niekorzystne, ze wskaźnikiem śmiertelności wynoszącym od 75% do 90%. Główną przyczyną zgonu jest niewydolność oddechowa. Rokowanie jest lepsze, gdy choroba jest związana z guzami łagodnymi i może nawet ustąpić po wycięciu guza.²²²³

Czynniki wpływające na rokowanie w pemfigusie paraneoplastycznym:²⁴²⁵

Charakter związanego nowotworu – pacjenci doświadczają szybkiej poprawy po wycięciu łagodnego guza, np. PNP związany z chorobą Castlemana
Obecność zarostowego zapalenia oskrzelików – koreluje z gorszym rokowaniem
Zajęcie płuc – występuje u 30-92,8% pacjentów, szacuje się, że jedna trzecia zgonów w PNP wynika z niewydolności płucnej

Zarostowe zapalenie oskrzelików może nadal się pogarszać pomimo poprawy objawów skórno-śluzówkowych po immunosupresji i resekcji guza. Szybka diagnoza i wczesne rozpoczęcie leczenia są obowiązkowe.²⁶

Pemfigoid pęcherzowy jako niepożądany efekt immunoterapii

Pemfigoid pęcherzowy stanowi rzadkie dermatologiczne zdarzenie niepożądane związane z układem immunologicznym, występujące podczas leczenia inhibitorami białka programowanej śmierci komórki 1 (PD-1) lub jego liganda (PD-L1). Ocena wyników leczenia nowotworów nie wykazała poprawy przeżycia u pacjentów, u których rozwinął się pemfigoid pęcherzowy podczas immunoterapii, w przeciwieństwie do innych typów toksyczności skórnej, w tym bielactwa.²⁷

Wyniki leczenia nowotworu udokumentowano dla 39 pacjentów z pemfigoidem pęcherzowym związanym z immunoterapią:²⁸

Całkowita odpowiedź (CR) lub częściowa odpowiedź (PR) została osiągnięta u 53,8% (21/39) pacjentów
Stabilizacja choroby (SD) wystąpiła u 7,7% (3/39) pacjentów
Progresja choroby (PD) nastąpiła u 38,8% (15/39) pacjentów

Wyniki te należy interpretować ostrożnie ze względu na retrospektywną analizę danych, która nie może ocenić wpływu czynników zakłócających (np. przedłużonej immunosupresji ogólnoustrojowej, przerwania immunoterapii) na wynik leczenia nowotworu. Dodatkowo, nie stwierdzono korelacji między nasileniem pemfigoidu pęcherzowego a wynikami leczenia nowotworu.²⁹

Czynniki predykcyjne remisji i nawrotów

Wskaźniki remisji

W medycynie weterynaryjnej, całkowitą remisję (CR) uzyskano u 26/40 psów (65%), które otrzymały leczenie. Spontaniczna remisja bez żadnego leczenia została zgłoszona tylko u 1/40 psów (3%). Dane te wskazują na kluczową rolę leczenia w osiągnięciu remisji.³⁰

W medycynie ludzkiej, powrót wyników bezpośredniego badania immunofluorescencyjnego (DIF) do wartości ujemnych może być przydatny do przewidywania trwałej remisji po odstawieniu leków.³¹

Czynniki ryzyka nawrotów

Nawroty mogą wystąpić u ponad 50% pacjentów z pemfigusem (w tym wariantów innych niż pemfigus zwyczajny). W jednym z badań stwierdzono, że następujące czynniki są związane z ryzykiem nawrotu:³²

Rozległe zajęcie powierzchni ciała (BSA)
Wysoki wskaźnik masy ciała pacjenta (BMI)
Duży stopień nasilenia choroby na początku, określony za pomocą wskaźnika obszaru choroby pemfigus (PDAI)
Opóźnione rozpoczęcie leczenia
Wysokie miana przeciwciał anty-DSG1 i anty-DSG3 po leczeniu

Podsumowanie czynników prognostycznych w pemfigusie

Chorobowość i śmiertelność w pemfigusie są związane z kilkoma kluczowymi czynnikami:³³³⁴

Zakres zajęcia skóry i błon śluzowych
Dawka kortykosteroidów wymagana do leczenia
Obecność chorób współistniejących wysokiego ryzyka
Wiek pacjenta – rokowanie jest gorsze u starszych pacjentów
Stan immunologiczny – pacjenci z obniżoną odpornością mają gorsze rokowanie
Rozległość lub nasilenie choroby – rozległa choroba wiąże się z gorszym rokowaniem

Rokowanie jest zwykle lepsze w przypadku zachorowania w dzieciństwie niż w wieku dorosłym. Pacjenci zdiagnozowani w wieku poniżej 65 lat mają lepsze rokowanie niż pacjenci zdiagnozowani w wieku ≥65 lat.³⁵³⁶

Dalsze badania mogą wyjaśnić podstawowe mechanizmy immunogenetyczne tego schorzenia, zidentyfikować pacjentów zagrożonych rozwojem pemfigusa oraz ustalić skuteczność i bezpieczeństwo istniejących środków terapeutycznych pod kątem ich potencjału do kontrolowania objawów bez wpływu na skuteczność przeciwnowotworową immunoterapii w przypadku pemfigoidu pęcherzowego związanego z immunoterapią.³⁷

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Materiały źródłowe

#1 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
Factors associated with survival in pemphigus have not yet been thoroughly addressed. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years (p0.001), presence of coronary heart disease (p=0.006), presence of cardiac arrhythmia (p=0.004), level of anti-desmoglein1 autoantibodies 100 U/mL (p=0.047) at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#2 An Updated Review of Pemphigus Diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540565/
PV represents a chronic, long-lasting condition that can be adequately controlled with medical therapy. The prognosis of PV has improved drastically over the decades as a result of recent advancements in corticosteroid and steroid-sparing treatments. […] Despite these advances in treatment, death still occurs in select patients with pemphigus, largely due to secondary infection. If left untreated, PV is typically fatal as a result of bacterial and viral infections and fluid and electrolyte imbalances. Most patients who are left untreated ultimately die within the first few years following diagnosis. Without adequate treatment, the reported mortality of PV is greater than 75%. […] Morbidity and mortality of PV is related to several factors, including the extent of mucocutaneous involvement, the dose of corticosteroid treatment required for treatment, and high-risk comorbidities. The prognosis of patients with PV is generally worse in elderly or immunocompromised patients and in those with extensive or severe disease. Patients who are diagnosed at 65 years of age are likely to fare better than those who are diagnosed at 65 years of age. […] The prognosis associated with PNP is largely unfavorable with a 75% to 90% mortality rate. Mortality associated with PNP can be attributed in part to the underlying malignancy that plays a central role in its pathogenesis.
#3 An Updated Review of Pemphigus Diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540565/
PV represents a chronic, long-lasting condition that can be adequately controlled with medical therapy. The prognosis of PV has improved drastically over the decades as a result of recent advancements in corticosteroid and steroid-sparing treatments. […] Despite these advances in treatment, death still occurs in select patients with pemphigus, largely due to secondary infection. If left untreated, PV is typically fatal as a result of bacterial and viral infections and fluid and electrolyte imbalances. Most patients who are left untreated ultimately die within the first few years following diagnosis. Without adequate treatment, the reported mortality of PV is greater than 75%. […] Morbidity and mortality of PV is related to several factors, including the extent of mucocutaneous involvement, the dose of corticosteroid treatment required for treatment, and high-risk comorbidities. The prognosis of patients with PV is generally worse in elderly or immunocompromised patients and in those with extensive or severe disease. Patients who are diagnosed at 65 years of age are likely to fare better than those who are diagnosed at 65 years of age. […] The prognosis associated with PNP is largely unfavorable with a 75% to 90% mortality rate. Mortality associated with PNP can be attributed in part to the underlying malignancy that plays a central role in its pathogenesis.
#4 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
The severity and natural history of pemphigus vulgaris are variable. Before the advent of steroids, most patients with pemphigus vulgaris died. Treatment with systemic steroids has reduced the mortality dramatically, to approximately 5-15%. […] If not properly treated, pemphigus vulgaris still is often fatal because of the susceptibility to infection and fluid and electrolyte disturbances. Mortality in patients with pemphigus vulgaris is three times higher than that in the general population. Most deaths occur during the first few years of disease; if the patient survives 5 years, the prognosis is good. Early disease probably is easier to control than widespread disease, and mortality may be higher if therapy is delayed. Complications secondary to the use of high-dose corticosteroids contribute to mortality as well.
#5 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
The severity and natural history of pemphigus vulgaris are variable. Before the advent of steroids, most patients with pemphigus vulgaris died. Treatment with systemic steroids has reduced the mortality dramatically, to approximately 5-15%. […] If not properly treated, pemphigus vulgaris still is often fatal because of the susceptibility to infection and fluid and electrolyte disturbances. Mortality in patients with pemphigus vulgaris is three times higher than that in the general population. Most deaths occur during the first few years of disease; if the patient survives 5 years, the prognosis is good. Early disease probably is easier to control than widespread disease, and mortality may be higher if therapy is delayed. Complications secondary to the use of high-dose corticosteroids contribute to mortality as well.
#6 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
Factors associated with survival in pemphigus have not yet been thoroughly addressed. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years (p0.001), presence of coronary heart disease (p=0.006), presence of cardiac arrhythmia (p=0.004), level of anti-desmoglein1 autoantibodies 100 U/mL (p=0.047) at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#7 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0263-4
Factors associated with survival in pemphigus have not yet been thoroughly addressed. Therefore, in the present study, risk factors for overall mortality in a large group of patients with pemphigus vulgaris and foliaceus were investigated. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years, presence of coronary heart disease, presence of cardiac arrhythmia, level of anti-desmoglein1 autoantibodies 100 U/mL at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#8 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] PV patients with an age of onset 65 years showed a higher risk for overall mortality, compared to patients with an age of onset 65 years (HR=9.37 (95% CI, 3.3-26.65), p0.001). […] In the PV group, association of coronary heart disease (HR=4.27 (95% CI, 1.5- 12.13), p=0.006) and cardiac arrhythmia (HR=6.19 (95% CI, 1.77-21.64), p=0.004) at diagnosis represented statistically significant risk factors for overall mortality in the initial univariate analysis. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis represented a risk factor for overall mortality in patients with PV (p=0.047), in the initial univariate analysis, but not when adjusted by age as continuous or dichotomous variable (p0.05).
#9 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0263-4
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] Presence of coronary heart disease and cardiac arrhythmia at diagnosis is associated with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-desmoglein 1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] In conclusion, in addition to common prognostic factors, including older age and cardiovascular comorbidities, our study signals the level of anti-desmoglein 1 autoantibodies as a candidate prediction factor for overall survival that should be reinforced in further studies.
#10 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] PV patients with an age of onset 65 years showed a higher risk for overall mortality, compared to patients with an age of onset 65 years (HR=9.37 (95% CI, 3.3-26.65), p0.001). […] In the PV group, association of coronary heart disease (HR=4.27 (95% CI, 1.5- 12.13), p=0.006) and cardiac arrhythmia (HR=6.19 (95% CI, 1.77-21.64), p=0.004) at diagnosis represented statistically significant risk factors for overall mortality in the initial univariate analysis. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis represented a risk factor for overall mortality in patients with PV (p=0.047), in the initial univariate analysis, but not when adjusted by age as continuous or dichotomous variable (p0.05).
#11 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] PV patients with an age of onset 65 years showed a higher risk for overall mortality, compared to patients with an age of onset 65 years (HR=9.37 (95% CI, 3.3-26.65), p0.001). […] In the PV group, association of coronary heart disease (HR=4.27 (95% CI, 1.5- 12.13), p=0.006) and cardiac arrhythmia (HR=6.19 (95% CI, 1.77-21.64), p=0.004) at diagnosis represented statistically significant risk factors for overall mortality in the initial univariate analysis. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis represented a risk factor for overall mortality in patients with PV (p=0.047), in the initial univariate analysis, but not when adjusted by age as continuous or dichotomous variable (p0.05).
#12 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] PV patients with an age of onset 65 years showed a higher risk for overall mortality, compared to patients with an age of onset 65 years (HR=9.37 (95% CI, 3.3-26.65), p0.001). […] In the PV group, association of coronary heart disease (HR=4.27 (95% CI, 1.5- 12.13), p=0.006) and cardiac arrhythmia (HR=6.19 (95% CI, 1.77-21.64), p=0.004) at diagnosis represented statistically significant risk factors for overall mortality in the initial univariate analysis. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis represented a risk factor for overall mortality in patients with PV (p=0.047), in the initial univariate analysis, but not when adjusted by age as continuous or dichotomous variable (p0.05).
#13 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0263-4
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] Presence of coronary heart disease and cardiac arrhythmia at diagnosis is associated with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-desmoglein 1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] In conclusion, in addition to common prognostic factors, including older age and cardiovascular comorbidities, our study signals the level of anti-desmoglein 1 autoantibodies as a candidate prediction factor for overall survival that should be reinforced in further studies.
#14 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
Factors associated with survival in pemphigus have not yet been thoroughly addressed. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years (p0.001), presence of coronary heart disease (p=0.006), presence of cardiac arrhythmia (p=0.004), level of anti-desmoglein1 autoantibodies 100 U/mL (p=0.047) at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#15 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0263-4
Factors associated with survival in pemphigus have not yet been thoroughly addressed. Therefore, in the present study, risk factors for overall mortality in a large group of patients with pemphigus vulgaris and foliaceus were investigated. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years, presence of coronary heart disease, presence of cardiac arrhythmia, level of anti-desmoglein1 autoantibodies 100 U/mL at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#16 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
Factors associated with survival in pemphigus have not yet been thoroughly addressed. […] In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset 65 years (p0.001), presence of coronary heart disease (p=0.006), presence of cardiac arrhythmia (p=0.004), level of anti-desmoglein1 autoantibodies 100 U/mL (p=0.047) at diagnosis and the survival of the patients. […] Multivariate analysis identified the age of onset 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. […] In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris.
#17 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4411722/
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] PV patients with an age of onset 65 years showed a higher risk for overall mortality, compared to patients with an age of onset 65 years (HR=9.37 (95% CI, 3.3-26.65), p0.001). […] In the PV group, association of coronary heart disease (HR=4.27 (95% CI, 1.5- 12.13), p=0.006) and cardiac arrhythmia (HR=6.19 (95% CI, 1.77-21.64), p=0.004) at diagnosis represented statistically significant risk factors for overall mortality in the initial univariate analysis. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-Dsg1 autoantibodies 100 U/mL at diagnosis represented a risk factor for overall mortality in patients with PV (p=0.047), in the initial univariate analysis, but not when adjusted by age as continuous or dichotomous variable (p0.05).
#18 Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0263-4
An age of onset 65 years is associated with a higher risk of overall mortality in patients with pemphigus vulgaris and foliaceus. […] Presence of coronary heart disease and cardiac arrhythmia at diagnosis is associated with a higher risk of overall mortality in patients with pemphigus vulgaris. […] A level of anti-desmoglein 1 autoantibodies 100 U/mL at diagnosis associates with a higher risk of overall mortality in patients with pemphigus vulgaris. […] In conclusion, in addition to common prognostic factors, including older age and cardiovascular comorbidities, our study signals the level of anti-desmoglein 1 autoantibodies as a candidate prediction factor for overall survival that should be reinforced in further studies.
#19 An Updated Review of Pemphigus Diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540565/
PV represents a chronic, long-lasting condition that can be adequately controlled with medical therapy. The prognosis of PV has improved drastically over the decades as a result of recent advancements in corticosteroid and steroid-sparing treatments. […] Despite these advances in treatment, death still occurs in select patients with pemphigus, largely due to secondary infection. If left untreated, PV is typically fatal as a result of bacterial and viral infections and fluid and electrolyte imbalances. Most patients who are left untreated ultimately die within the first few years following diagnosis. Without adequate treatment, the reported mortality of PV is greater than 75%. […] Morbidity and mortality of PV is related to several factors, including the extent of mucocutaneous involvement, the dose of corticosteroid treatment required for treatment, and high-risk comorbidities. The prognosis of patients with PV is generally worse in elderly or immunocompromised patients and in those with extensive or severe disease. Patients who are diagnosed at 65 years of age are likely to fare better than those who are diagnosed at 65 years of age. […] The prognosis associated with PNP is largely unfavorable with a 75% to 90% mortality rate. Mortality associated with PNP can be attributed in part to the underlying malignancy that plays a central role in its pathogenesis.
#20 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
The severity and natural history of pemphigus vulgaris are variable. Before the advent of steroids, most patients with pemphigus vulgaris died. Treatment with systemic steroids has reduced the mortality dramatically, to approximately 5-15%. […] If not properly treated, pemphigus vulgaris still is often fatal because of the susceptibility to infection and fluid and electrolyte disturbances. Mortality in patients with pemphigus vulgaris is three times higher than that in the general population. Most deaths occur during the first few years of disease; if the patient survives 5 years, the prognosis is good. Early disease probably is easier to control than widespread disease, and mortality may be higher if therapy is delayed. Complications secondary to the use of high-dose corticosteroids contribute to mortality as well.
#21 Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease | Actas Dermo-SifiliogrÃ¡ficas
https://www.actasdermo.org/es-paraneoplastic-pemphigus-a-life-threatening-autoimmune-articulo-S1578219017303761
Paraneoplastic pemphigus is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. […] Prognosis depends on the nature of the associated tumor. Some patients experience rapid improvement after excision of a benign tumor, such as PNP associated to Castleman’s disease. However, malignant tumors are often accompanied not only by higher mortality from the associated malignancy but also because the PNP can be severe and often recalcitrant. […] The overall prognosis of PNP is poor. The mortality rate ranges from 75% to 90%, being respiratory failure the main cause of death. The prognosis is better when the disease is associated with benign tumors and may even remit when tumors are excised.
#22 Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease | Actas Dermo-SifiliogrÃ¡ficas
https://www.actasdermo.org/es-paraneoplastic-pemphigus-a-life-threatening-autoimmune-articulo-S1578219017303761
Paraneoplastic pemphigus is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. […] Prognosis depends on the nature of the associated tumor. Some patients experience rapid improvement after excision of a benign tumor, such as PNP associated to Castleman’s disease. However, malignant tumors are often accompanied not only by higher mortality from the associated malignancy but also because the PNP can be severe and often recalcitrant. […] The overall prognosis of PNP is poor. The mortality rate ranges from 75% to 90%, being respiratory failure the main cause of death. The prognosis is better when the disease is associated with benign tumors and may even remit when tumors are excised.
#23 Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review | BMC Veterinary Research | Full Text
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-020-02677-w
Pemphigus is the term used to describe a group of rare mucocutaneous autoimmune bullous diseases characterized by flaccid blisters and erosions of the mucous membranes and/or skin. […] In animals, the partial-to-complete remission of pemphigus vulgaris and pemphigus vegetans has been achieved with high dose glucocorticoid therapy, with or without adjunct immunosuppressants; the prognosis is grave for paraneoplastic pemphigus. […] Overall, a complete remission (CR) was obtained in 26/40 dogs (65%) that received treatment. […] A spontaneous remission without any treatment was only reported in 1/40 dogs (3%). […] The prognosis of paraneoplastic pemphigus in humans is poor and its mortality rate is high, the latter ranging from 75 to 90% of patients with the mean survival rate of less than 1 year. […] In all three dogs, the paraneoplastic pemphigus had a fatal outcome.
#24 Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease | Actas Dermo-SifiliogrÃ¡ficas
https://www.actasdermo.org/es-paraneoplastic-pemphigus-a-life-threatening-autoimmune-articulo-S1578219017303761
Paraneoplastic pemphigus is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. […] Prognosis depends on the nature of the associated tumor. Some patients experience rapid improvement after excision of a benign tumor, such as PNP associated to Castleman’s disease. However, malignant tumors are often accompanied not only by higher mortality from the associated malignancy but also because the PNP can be severe and often recalcitrant. […] The overall prognosis of PNP is poor. The mortality rate ranges from 75% to 90%, being respiratory failure the main cause of death. The prognosis is better when the disease is associated with benign tumors and may even remit when tumors are excised.
#25 Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease | Actas Dermo-SifiliogrÃ¡ficas
https://www.actasdermo.org/es-paraneoplastic-pemphigus-a-life-threatening-autoimmune-articulo-S1578219017303761
Bronchiolitis obliterans correlates with poor prognosis. Pulmonary involvement occurs in 30-92.8% of patients and it is estimated that one-third of the deaths in PNP are due to pulmonary insufficiency. It is known that constrictive bronchiolitis can continue to worsen despite improvement in muco-cutaneous manifestations after immunosuppressive therapy and resection of tumor. A prompt diagnosis and early introduction of treatment are mandatory.
#26 Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease | Actas Dermo-SifiliogrÃ¡ficas
https://www.actasdermo.org/es-paraneoplastic-pemphigus-a-life-threatening-autoimmune-articulo-S1578219017303761
Bronchiolitis obliterans correlates with poor prognosis. Pulmonary involvement occurs in 30-92.8% of patients and it is estimated that one-third of the deaths in PNP are due to pulmonary insufficiency. It is known that constrictive bronchiolitis can continue to worsen despite improvement in muco-cutaneous manifestations after immunosuppressive therapy and resection of tumor. A prompt diagnosis and early introduction of treatment are mandatory.
#27 Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature | HTML | Acta Dermato-Venereologica
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3740
Bullous pemphigoid constitutes a rare dermatological immune-related adverse event of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. […] Assessment of tumour outcome did not reveal improved survival in patients developing bullous pemphigoid during immunotherapy, as suggested for other types of skin toxicity, including vitiligo. […] Better understanding of the pathogenetic mechanism and prognostic implications of this increasingly-reported adverse event is essential in order to establish optimal diagnostic and therapeutic management of these patients. […] The clinical findings of drug-associated BP resembled those of classic disease, including a prodromal, pruritic, papular or eczematous eruption followed by moderate-to-severe skin blistering in 87.9% and mucosal involvement in 15.5% of cases.
#28 Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature | HTML | Acta Dermato-Venereologica
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3740
A delayed onset of cutaneous irAEs (3 months) is common and has also been described for other dermatological irAEs, including granulomatous reactions and erythema multiforme. […] Tumour outcome was documented for 39 patients. Complete response (CR) or partial response (PR) was achieved in 53.8% (21/39) of patients, 7.7% (3/39) of them experienced stable disease (SD) and 38.8% (15/39) had progressive disease (PD). […] However, they should be interpreted with caution due to the retrospective analysis of the data, which cannot assess the effect of confounding factors (e.g. prolonged systemic immunosuppression, withdrawal of immunotherapy) on tumour outcome. […] In addition, tumour outcome was not found to be correlated with BP severity. […] Given the small number of patients undergoing re-challenge, it is not possible to draw conclusions regarding potential recurrence after recommencing immunotherapy, and this should depend on blistering control and perceived benefits.
#29 Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature | HTML | Acta Dermato-Venereologica
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3740
A delayed onset of cutaneous irAEs (3 months) is common and has also been described for other dermatological irAEs, including granulomatous reactions and erythema multiforme. […] Tumour outcome was documented for 39 patients. Complete response (CR) or partial response (PR) was achieved in 53.8% (21/39) of patients, 7.7% (3/39) of them experienced stable disease (SD) and 38.8% (15/39) had progressive disease (PD). […] However, they should be interpreted with caution due to the retrospective analysis of the data, which cannot assess the effect of confounding factors (e.g. prolonged systemic immunosuppression, withdrawal of immunotherapy) on tumour outcome. […] In addition, tumour outcome was not found to be correlated with BP severity. […] Given the small number of patients undergoing re-challenge, it is not possible to draw conclusions regarding potential recurrence after recommencing immunotherapy, and this should depend on blistering control and perceived benefits.
#30 Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review | BMC Veterinary Research | Full Text
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-020-02677-w
Pemphigus is the term used to describe a group of rare mucocutaneous autoimmune bullous diseases characterized by flaccid blisters and erosions of the mucous membranes and/or skin. […] In animals, the partial-to-complete remission of pemphigus vulgaris and pemphigus vegetans has been achieved with high dose glucocorticoid therapy, with or without adjunct immunosuppressants; the prognosis is grave for paraneoplastic pemphigus. […] Overall, a complete remission (CR) was obtained in 26/40 dogs (65%) that received treatment. […] A spontaneous remission without any treatment was only reported in 1/40 dogs (3%). […] The prognosis of paraneoplastic pemphigus in humans is poor and its mortality rate is high, the latter ranging from 75 to 90% of patients with the mean survival rate of less than 1 year. […] In all three dogs, the paraneoplastic pemphigus had a fatal outcome.
#31 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
Morbidity and mortality are related to the extent of disease, the maximum dose of prednisolone required to induce remission, and the presence of other diseases. The outlook is worse in older patients and in patients with extensive disease. Prognosis is usually better in childhood than in adulthood. […] Reversion of DIF to negative can be useful for predicting sustained remission after withdrawal of medication. […] Relapses may occur in more than 50% of patients with pemphigus (including variants other than pemphigus vulgaris). In one study, the following were found to be risk factors for relapse: Extensive body surface area (BSA) involvement, High patient body mass index (BMI), High degree of severity at onset, as determined by the Pemphigus Disease Area Index (PDAI), Delayed provision of treatment, High titers of anti-DSG1 and anti-DSG3 after treatment.
#32 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
Morbidity and mortality are related to the extent of disease, the maximum dose of prednisolone required to induce remission, and the presence of other diseases. The outlook is worse in older patients and in patients with extensive disease. Prognosis is usually better in childhood than in adulthood. […] Reversion of DIF to negative can be useful for predicting sustained remission after withdrawal of medication. […] Relapses may occur in more than 50% of patients with pemphigus (including variants other than pemphigus vulgaris). In one study, the following were found to be risk factors for relapse: Extensive body surface area (BSA) involvement, High patient body mass index (BMI), High degree of severity at onset, as determined by the Pemphigus Disease Area Index (PDAI), Delayed provision of treatment, High titers of anti-DSG1 and anti-DSG3 after treatment.
#33 An Updated Review of Pemphigus Diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540565/
PV represents a chronic, long-lasting condition that can be adequately controlled with medical therapy. The prognosis of PV has improved drastically over the decades as a result of recent advancements in corticosteroid and steroid-sparing treatments. […] Despite these advances in treatment, death still occurs in select patients with pemphigus, largely due to secondary infection. If left untreated, PV is typically fatal as a result of bacterial and viral infections and fluid and electrolyte imbalances. Most patients who are left untreated ultimately die within the first few years following diagnosis. Without adequate treatment, the reported mortality of PV is greater than 75%. […] Morbidity and mortality of PV is related to several factors, including the extent of mucocutaneous involvement, the dose of corticosteroid treatment required for treatment, and high-risk comorbidities. The prognosis of patients with PV is generally worse in elderly or immunocompromised patients and in those with extensive or severe disease. Patients who are diagnosed at 65 years of age are likely to fare better than those who are diagnosed at 65 years of age. […] The prognosis associated with PNP is largely unfavorable with a 75% to 90% mortality rate. Mortality associated with PNP can be attributed in part to the underlying malignancy that plays a central role in its pathogenesis.
#34 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
Morbidity and mortality are related to the extent of disease, the maximum dose of prednisolone required to induce remission, and the presence of other diseases. The outlook is worse in older patients and in patients with extensive disease. Prognosis is usually better in childhood than in adulthood. […] Reversion of DIF to negative can be useful for predicting sustained remission after withdrawal of medication. […] Relapses may occur in more than 50% of patients with pemphigus (including variants other than pemphigus vulgaris). In one study, the following were found to be risk factors for relapse: Extensive body surface area (BSA) involvement, High patient body mass index (BMI), High degree of severity at onset, as determined by the Pemphigus Disease Area Index (PDAI), Delayed provision of treatment, High titers of anti-DSG1 and anti-DSG3 after treatment.
#35 An Updated Review of Pemphigus Diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540565/
PV represents a chronic, long-lasting condition that can be adequately controlled with medical therapy. The prognosis of PV has improved drastically over the decades as a result of recent advancements in corticosteroid and steroid-sparing treatments. […] Despite these advances in treatment, death still occurs in select patients with pemphigus, largely due to secondary infection. If left untreated, PV is typically fatal as a result of bacterial and viral infections and fluid and electrolyte imbalances. Most patients who are left untreated ultimately die within the first few years following diagnosis. Without adequate treatment, the reported mortality of PV is greater than 75%. […] Morbidity and mortality of PV is related to several factors, including the extent of mucocutaneous involvement, the dose of corticosteroid treatment required for treatment, and high-risk comorbidities. The prognosis of patients with PV is generally worse in elderly or immunocompromised patients and in those with extensive or severe disease. Patients who are diagnosed at 65 years of age are likely to fare better than those who are diagnosed at 65 years of age. […] The prognosis associated with PNP is largely unfavorable with a 75% to 90% mortality rate. Mortality associated with PNP can be attributed in part to the underlying malignancy that plays a central role in its pathogenesis.
#36 Pemphigus Vulgaris: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1064187-overview
Morbidity and mortality are related to the extent of disease, the maximum dose of prednisolone required to induce remission, and the presence of other diseases. The outlook is worse in older patients and in patients with extensive disease. Prognosis is usually better in childhood than in adulthood. […] Reversion of DIF to negative can be useful for predicting sustained remission after withdrawal of medication. […] Relapses may occur in more than 50% of patients with pemphigus (including variants other than pemphigus vulgaris). In one study, the following were found to be risk factors for relapse: Extensive body surface area (BSA) involvement, High patient body mass index (BMI), High degree of severity at onset, as determined by the Pemphigus Disease Area Index (PDAI), Delayed provision of treatment, High titers of anti-DSG1 and anti-DSG3 after treatment.
#37 Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature | HTML | Acta Dermato-Venereologica
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3740
Further studies may clarify the underlying immunogenetic mechanisms of this condition, identify patients at risk of development of BP, and ascertain the efficacy and safety of existing therapeutic agents in terms of their potential to control symptoms without affecting the antitumour efficacy of immunotherapy.