SKIN 
 

December 2018     Volume 2 Supplemental Issue  
 

Copyright 2018 The National Society for Cutaneous Medicine 97 

RISING DERM STARS 
 

 
Association of Pemphigus and Pemphigoid with Osteoporosis and 
Pathological Fractures 
Raj Chovatiya MD, PhD1, Jonathan Silverberg MD, PhD, MPH1 
 
1Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 

 
 
Background: Pemphigus and pemphigoid 
are two groups of autoimmune bullous 
disease (AIBD) associated with high 
morbidity and mortality. While there is no cure 
for either condition, a mainstay for treatment 
is long-term systemic corticosteroids that can 
decrease bone mineral density (BMD). 
Patients with pemphigus and pemphigoid 
likely have additional risk factors for 
decreased BMD, including chronic 
inflammation. 
 
Osteoporosis and skeletal fractures resulting 
from decreased BMD can lead to significant 
morbidity, hospitalization, decreased quality 
of life, and mortality. However, no large-scale 
studies have rigorously examined the 
association of AIBD with osteoporosis and 
fractures. 
 
Objective: The goal of our study was to 
determine whether pemphigus and 
pemphigoid are associated with osteoporosis 
and fracture in the U.S. population and how 
this affects admission rates and cost of care. 
 
Methods: We performed a cross-sectional 
study of 198,102,435 children and adults, 
including 4,502 with pemphigus and 8,863 
with pemphigoid, from the 2006-2012 
National Emergency Department Sample 
(NEDS), which is comprised of 20% of all 
emergency care visits throughout the United 
States. 

Results: Patients with pemphigus or 
pemphigoid were more likely to be female, 
older, evenly distributed across income 
quartiles, use Medicare as the primary 
source of payment, and have a history of 
long-term steroid use. A pooled analysis 
across all 7 years showed that patients with 
pemphigus had significantly higher odds 
(multivariate logistic regression including 
age, sex, primary payer, income quartile, 
history of long-term steroids; OR, 95% CI) of 
diagnosis with osteopenia (2.200, 1.590-
3.045), osteoporosis (2.536, 2.159-2.978), 
osteomalacia (29.699, 4.049-217.834), and 
pathologic fracture (2.035, 1.422-2.912)  
 
Similarly, patients with pemphigoid had 
significantly higher odds of diagnosis with 
osteoporosis (1.550, 1.392-1.727) 
and pathologic fracture (1.517, 1.222-1.884). 
Patients with pemphigus additionally had 
significantly higher odds of diagnosis with 
femur fracture (1.459, 1.125-1.893) and 
vertebral fracture (1.464 1.060-2.023). 
 
Significant two-way interactions were 
detected between both pemphigus and 
pemphigoid and history of long-term steroid 
use on osteopenia, osteoporosis, and 
pathologic fracture. The rate of inpatient 
admission (% frequency, 95% CI) in patients 
with both pemphigus and fracture (96.4, 89.4-
100.0) and pemphigoid and fracture (90.9, 



SKIN 
 

December 2018     Volume 2 Supplemental Issue  
 

Copyright 2018 The National Society for Cutaneous Medicine 98 

80.4-100.0) was significantly higher than in 
those without fracture. The yearly inflation 
adjusted cost of combined ED and inpatient 
care was consistently and significantly higher 
in patients with pemphigus or pemphigoid 
and fracture compared to those without 
fracture. 
 
Limitations: Data on severity and treatments 
of pemphigus and pemphigoid were not 
available. 
 
Conclusion: Pemphigus and Pemphigoid 
were associated with an increased risk of 
osteoporosis and pathologic fractures. This 
remained significant even after controlling for 
history of long-term steroid use, suggesting 
other disease intrinsic and extrinsic factors 
may underlie this increased risk (e.g. chronic 
inflammation, medication, lifestyle). Patients 
with either pemphigus or pemphigoid and 
fracture also had higher admission rates and 
higher overall inflation adjusted cost of care. 
We propose that patients with pemphigus 
and pemphigoid constitute a significant, 
previously underrecognized public health 
burden due to risk for fractures, and they may 
benefit from early inventions (i.e. early bone 
density scans, adjustments in steroid dose, 
vitamin supplementation, referral to 
endocrinologist) from their primary physician 
– the dermatologist.