Serious infections in hospitalized patients with psoriasis in the United States

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1 FROM THE DERMATOLOGY FOUNDATION Serious infections in hospitalized patients with psoriasis in the United States Derek Y. Hsu, BA, a Kenneth Gordon, MD, a andjonathani.silverberg,md,phd,mph a,b,c Chicago, Illinois Background: Patients with psoriasis have multiple risk factors for serious infections, including immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions. Objective: We sought to determine rates and predictors of serious infections in hospitalized psoriasis patients and quantify costs of care, length of stay, and mortality. Methods: We conducted a cross-sectional study of the Nationwide Inpatient Sample from 2002 to 2012, containing a representative 20% sample of all hospitalizations in the United States. Results: In multivariate logistic regression models, psoriasis was associated with multiple serious infections, including methicillin-resistant Staphylococcus aureus (odds ratio [OR] 1.76, 95% confidence intervals [CI] ), cellulitis (OR 3.21, 95% CI ), herpes simplex virus infection (OR 2.21, 95% CI ), infectious arthritis (OR 1.82, 95% CI ), osteomyelitis (OR 1.31, 95% CI ), meningitis (OR 1.31, 95% CI ), encephalitis (OR 1.22, 95% CI ), and tuberculosis (OR 1.34, 95% CI ). Among patients with psoriasis, rates of serious infections increased over all time intervals analyzed (P =.01) and were significantly higher compared with those without psoriasis across all time intervals (P \.0001). The mean length of stay ( days) and cost of care ($13,291 6 $166) for psoriasis patients with serious infections was higher than that of psoriasis patients without serious infections ( days; $11,003 6 $96; P \.0001). Limitations: The study was limited to inpatients. Medication data were not available. Conclusion: Serious infections are increasing in incidence in US inpatients with psoriasis. ( J Am Acad Dermatol 2016;75: ) Key words: biologics; cost of care; hospitalization; length of stay; methotrexate; psoriasis; serious infection. Psoriasis is a chronic, immune-mediated, systemic inflammatory skin disorder with substantial morbidity and mortality affecting over 7 million adults in the United States. 1 Psoriasis is associated with impaired barrier function and immune dysregulation, both of the innate and adaptive immune system. 2-4 Localized and mild cases can be treated topically, although moderate to severe cases of psoriasis often require the use of systemic therapies. These therapeutics, which include conventional systemic immunosuppressants or the newer biologics, can be highly efficacious in managing psoriasis. 5,6 Although biologics should reduce inherent infectious risk by controlling the inflammatory process and subsequently reducing disease severity, these effects may be immunosuppressing and increase risk of infection in other ways. Conflicting results regarding whether these biologics From the Departments of Dermatology, a Preventive Medicine, b and Medical Social Sciences, c Northwestern University Feinberg School of Medicine. This publication was made possible with support from the Agency for Healthcare Research and Quality, grant number K12HS023011, the Dermatology Foundation. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Conflicts of interest: None declared. Presented in part at the Society for Investigative Dermatology 2016 Annual Meeting in Scottsdale, AZ on May 12, Accepted for publication April 4, Reprint requests: Jonathan I. Silverberg, MD, PhD, MPH, Department of Dermatology, Northwestern University Feinberg School of Medicine, Suite 1600, 676 N St Clair St, Chicago, IL JonathanISilverberg@gmail.com. Published online June 17, /$36.00 Ó 2016 by the American Academy of Dermatology, Inc

2 288 Hsu, Gordon, and Silverberg JAM ACAD DERMATOL AUGUST 2016 affect the rate of serious infections in patients with psoriasis have been observed. 7,8 In addition, patients with psoriasis may have other risk factors for serious infections, including higher prevalences of diabetes mellitus, overweight, and obesity. 9 We sought to quantify the frequency and inpatient burden of serious infections in hospitalized patients with psoriasis in the United States. METHODS The 2002 to 2012 Nationwide Inpatient Sample (NIS) was analyzed. The NIS is sponsored by the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ). 10 Each year of NIS contains an approximately 20% stratified representative sample of all hospitalizations in the United States. Sample weights were created by NIS CAPSULE SUMMARY that factored the sampling design of hospitals. These sample weights were needed to provide representative estimates of hospital discharges across the United States. All data were deidentified and no attempts were made to identify any of the individuals in the database. Patient consent was not obtained as the databases were received deidentified. All parties with access to HCUP were compliant to the HCUP formal data use agreement. The study was approved by the institutional review board at Northwestern University. Selection of psoriasis The databases were searched for a primary and/or secondary discharge diagnosis of psoriasis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The primary diagnosis was defined in NIS as the condition chiefly responsible for admission to the hospital, with up to 24 secondary diagnoses for each discharge. An ICD-9-CM code of corresponds to psoriasis. ICD-9-CM codes for psoriasis were previously validated. 11,12 The control group included all patients without any diagnosis of psoriasis, yielding a representative cohort of hospitalized patients in the United States. Identification of serious infections Serious infections were selected based on those previously studied with psoriasis 8 and other infectious causes that were considered a priori with d d d Patients with psoriasis have multiple risk factors for serious infections, such as immune dysregulation and systemic immunosuppressants. Serious infections are increasing in incidence in hospitalized patients with psoriasis, with higher rates among nonwhite and nonprivately insured patients. Hospitalized patients with psoriasis require close monitoring for infection. distinct ICD-9-CM codes for analysis. A serious infection was considered present with either a primary or secondary diagnosis of the disease. Some infections were pre-coded through the NIS Clinical Classification Software AHRQ (Rockville, MD). All variables were coded exclusively through ICD-9-CM codes. Mortality Adjusted mortality was calculated for patients with psoriasis with each type of serious infection. Mortality was adjusted for sex and race based on the US population composition according to the US Census. 13 Data processing and statistical analysis All data processing and statistical analyses were performed using software (SAS, Version 9.4, SAS Institute, Cary, NC). To determine the predictors of inpatient mortality in psoriasis compared with no psoriasis, weighted multivariate logistic regression models were constructed with mortality as the dependent variable. The independent variables included age (0-17, 18-39, 40-59, 60-79, $80 years), sex (male, female), race/ethnicity (white, black, Hispanic, Asian, Native American, multiracial/other), median annual income of the hospital ZIP code (quartiles), health insurance coverage (Medicare, Medicaid, private, self-pay, no charge, other) number of chronic conditions (0-1, 2-5, $6), season of admission (winter, spring, summer, autumn), hospital location (metropolitan $1 million, fringe/metropolitan \1 million, micropolitan, not metropolitan or micropolitan; Northeast, Midwest, South, and West), teaching status (yes, no), bed size (small, medium, large), and the full panel of serious infections. Independent variables were chosen to assess for sociodemographic disparities, as disparities in hospitalization rates and mortality have been observed in other dermatologic disorders, such as pemphigus. 14 Micropolitan counties were defined as an urban cluster population between 10,000 and 49,999 people. 15 A chronic condition was defined as a condition lasting at least 12 months and meeting at least 1 of the following criteria: it places limitations on self-care or requires continuous treatment/therapy. Multivariate logistic regression models used stepwise selection from the abovementioned covariates (alpha = 0.1). Complete case

3 JAM ACAD DERMATOL VOLUME 75, NUMBER 2 Hsu, Gordon, and Silverberg 289 Abbreviations used: CI: confidence interval HCUP: Healthcare Cost and Utilization Project ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification LOS: length of stay MRSA: methicillin-resistant Staphylococcus aureus MSSA: methicillin-sensitive Staphylococcus aureus NIS: Nationwide Inpatient Sample OR: odds ratio analysis was performed. A 2-sided P value less than.05 was considered statistically significant. Weighted prevalences of hospitalization with a primary and/or secondary diagnosis of psoriasis were determined. Associations between psoriasis and serious infections were tested using SURVEY procedures which adjust for survey weighting and sampling clusters and strata. To determine the associations of serious infections, weighted multivariate logistic regression models with stepwise selection were constructed with serious infections as the dependent variable. The aforementioned sociodemographic factors along with diabetes mellitus and obesity were the independent variables. For sensitivity analyses, psoriasis patients with and without psoriatic arthritis (ICD-9-CM 696.0) were also analyzed. Analysis of variance was used to compare frequency of serious infections. Post hoc comparisons for the frequencies of serious infections in patients with psoriasis were performed between 2002 and 2003, 2004 and 2005, 2006 and 2007, 2008 and 2009, and 2010 and 2012 using Tukey method. In each of these time intervals, post hoc comparison for the frequencies of serious infections were performed between patients with and without psoriasis. The cost for inpatient care was calculated based on the total charge of the hospitalization and the cost-tocharge ratio estimated by HCUP. All costs were adjusted for inflation to the year 2014 according to the Consumer Price Index from the US Bureau of Labor Statistics. 16 Summary statistics were generated for length of stay (LOS), total charge, and estimated inflation-adjusted cost of care, including sum, mean, SD, minimum, maximum, and median. RESULTS Overall, there were 87,039,711 discharges captured in the NIS between the years 2002 and There were 2738 primary admissions for psoriasis and 184,508 secondary diagnoses of psoriasis (weighted: 13,051 and 885,115, respectively). Patients with psoriasis (age years) were older than patients without psoriasis (age years), 47.5% female, and mostly white (Table I). Serious infections represented 28.2% of all hospitalizations in patients with psoriasis, but only 21.0% of hospitalizations in patients without psoriasis. In survey-weighted logistic regression models controlling for age, race, and sex, psoriasis was positively significantly associated with any serious infection (adjusted odds ratio [OR] 1.30, 95% confidence interval [CI] ), particularly cellulitis (OR 3.21, 95% CI ), herpes simplex virus infection (OR 2.21, 95% CI ), any fungal infection (OR 2.02, 95% CI ), infectious arthritis (OR 1.82, 95% CI ), methicillin-resistant Staphylococcus aureus (MRSA) (OR 1.76, 95% CI ), methicillin-sensitive S aureus (MSSA) (OR 1.26, 95% CI ), Clostridium difficile infection (OR 1.15, 95% CI ), any viral infection (OR 1.56, 95% CI ), tuberculosis (OR 1.34, 95% CI ), osteomyelitis (OR 1.31, 95% CI ), meningitis (OR 1.31, 95% CI ), encephalitis (OR 1.22, 95% CI ), influenza (OR 1.17, 95% CI ), septicemia (OR 1.05, 95% CI ), and enterocolitis (OR 1.05, 95% CI ) (Table II). In sensitivity analyses, OR remained unchanged when analyzing patients with psoriasis without a diagnosis of psoriatic arthritis. Associations of serious infection in inpatients with psoriasis In multivariate models with stepwise selection, predictors of 1 or more serious infections in patients with psoriasis included increasing age (18-39 years OR 0.92, 95% CI ; years OR 1.08, 95% CI ; years OR 1.15, 95% CI ; $80 years OR 1.69, 95% CI ), season (winter OR 1.06, 95% CI ; summer OR 1.03, 95% CI ; fall OR 1.06, 95% CI ), female sex (OR 1.16, 95% CI ), race/ethnicity (black OR 1.13, 95% CI ; Hispanic OR 1.04, 95% CI ; Asian OR 1.05, 95% CI ; Native American OR 1.20, 95% CI ), lower median household income (quartile 1: OR 1.10, 95% CI ; quartile 2: OR 1.03, 95% CI ; quartile 3: OR 1.04, 95% CI ), insurance status (Medicare OR 1.25, 95% CI ; Medicaid OR 1.20, 95% CI ; self-pay OR 1.18, 95% CI ), decreasing number of chronic conditions (2-5: OR 0.68, 95% CI ; $6: OR 0.63, 95% CI ), hospital location (fringe/metropolitan county \1 million people OR 0.98, 95% CI ; micropolitan county OR 0.96, 95% CI ), region of the United States (Northeast OR 0.81, 95% CI ; Midwest OR 0.96, 95% CI ),

4 290 Hsu, Gordon, and Silverberg JAM ACAD DERMATOL AUGUST 2016 Table I. Patient demographics Variable No psoriasis Psoriasis Age, y (SD) 47.9 (0.1) 59.9 (0.2) Female 50,523,410 (58.6%) 89,087 (47.5%) Race White 45,441,511 (66.3%) 124,408 (80.7%) Black 9,717,335 (14.2%) 10,186 (6.6%) Hispanic 8,880,800 (12.9%) 11,550 (7.5%) Asian 1,807,683 (2.6%) 3262 (2.1%) Native American 417,594 (0.6%) 798 (0.5%) Multiracial/other 2,323,830 (3.4%) 3907 (2.6%) diabetes mellitus (OR 1.14, 95% CI ), and obesity (OR 1.23, 95% CI ) (Table III). Trends of serious infections Among patients with a diagnosis of psoriasis, rates of serious infections overall increased over all time intervals (P =.01). In particular, rates of urinary tract infection, enterocolitis, encephalitis, any viral infection, any fungal infection, MRSA, and C difficile infection increased over all time intervals (Fig 1). All other serious infections demonstrated increased rates in at least 1 time interval. However, multiple causes of infections also increased in patients without psoriasis. Therefore, we examined the rates of increase in those with and without psoriasis. Overall, rates of serious infections were significantly higher in patients with psoriasis compared with those without psoriasis across all time intervals (analysis of variance; P \.0001). In particular, patients with psoriasis had higher rates of pneumonia (P =.01), cellulitis (P \.0001), diverticulitis (P \.0001), osteomyelitis (P =.01), infectious arthritis (P \.0001), any viral infection (P =.02), any fungal infection (P\.0001), tuberculosis (P\.0001), MRSA (P \.0001), and MSSA (P \.0001) at all time intervals (Supplemental Fig 1). In contrast, patients with psoriasis did not have higher rates of appendicitis, urinary tract infection, pyelonephritis, or influenza at any time interval. All other infections occurred at a significantly higher rate in at least 1 time interval in patients with psoriasis compared with patients without psoriasis. Impact of serious infections on length of hospitalization Among patients with psoriasis, the mean LOS of patients with any serious infection ( days) was higher than that of patients with psoriasis without serious infections ( days; P \.0001). Mean LOS for serious infections in Table II. Associations between psoriasis and serious infections Type of infection Adjusted OR [95% CI] P value Any serious infection 1.30 [ ] \.0001 Cellulitis 3.21 [ ] \.0001 HSV infection 2.21 [ ] \.0001 Any fungal infection 2.02 [ ] \.0001 Infectious arthritis 1.82 [ ] \.0001 MRSA 1.76 [ ] \.0001 Viral infection 1.56 [ ] \.0001 Tuberculosis 1.34 [ ] \.0001 Osteomyelitis 1.31 [ ] \.0001 Meningitis 1.31 [ ] \.0001 MSSA 1.26 [ ] \.0001 Necrotizing fasciitis 1.24 [ ].2 Encephalitis 1.22 [ ].03 Influenza 1.17 [ ].01 Clostridium difficile infection 1.15 [ ].005 Septicemia 1.05 [ ].003 Enterocolitis 1.05 [ ].02 Pyelonephritis 1.04 [ ].5 Endocarditis 1.04 [ ].7 Acute bronchitis 1.01 [ ].7 Diverticulitis 0.99 [ ].9 Urinary tract infection 0.98 [ ].03 Pneumonia 0.96 [ ].0004 Peritonitis/intestinal abscess 0.92 [ ].02 Pseudomonas infection 0.90 [ ].2 Gangrene 0.71 [ ].2 Appendicitis 0.58 [ ] \.0001 CI, Confidence interval; HSV, herpes simplex virus; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillinsensitive Staphylococcus aureus; OR, odds ratio. patients with psoriasis that were higher than mean LOS for patients with psoriasis without serious infections included herpes simplex virus infection, any fungal infection, infectious arthritis, any viral infection, tuberculosis, meningitis, necrotizing fasciitis, encephalitis, influenza, septicemia, enterocolitis, endocarditis, diverticulitis, urinary tract infection, pneumonia, peritonitis or intestinal abscess, gangrene, MRSA, MSSA, Pseudomonas, and C difficile infection (Table IV). Impact of serious infections on cost of care The mean cost of care for patients with psoriasis and any serious infection ($13,291 6 $166) was significantly higher than for patients with psoriasis without serious infections ($11,003 6 $96; P \.0001). Mean costs of care for serious infections in patients with psoriasis that were higher than the average cost of hospitalization for patients with psoriasis without serious infections included any fungal infection, infectious arthritis, any viral

5 JAM ACAD DERMATOL VOLUME 75, NUMBER 2 Hsu, Gordon, and Silverberg 291 Table III. Associations of serious infections in inpatients with psoriasis Variable Adjusted OR [95% CI] P value Age, y [ref] e [ ] [ ] [ ].0002 $ [ ] \.0001 Season Winter 1.06 [ ] \.0001 Spring 1.00 [ref] e Summer 1.03 [ ].004 Fall 1.06 [ ] \.0001 Gender Female 1.16 [ ] \.0001 Male 1.00 [ref] e Race White 1.00 [ref] e Black 1.13 [ ] \.0001 Hispanic 1.04 [ ].0003 Asian 1.05 [ ].01 Native American 1.20 [ ] \.0001 Other 1.01 [ ].8 Income quartile [ ] \ [ ] [ ] \ [ref] e Insurance Medicare 1.25 [ ] \.0001 Medicaid 1.20 [ ] \.0001 Private insurance 1.00 [ref] e Self-pay 1.18 [ ] \.0001 No charge 1.06 [ ].3 Other 0.99 [ ].5 No. of chronic conditions [ref] e [ ] \.0001 $ [ ] \.0001 Hospital location Metropolitan $1million 1.00 [ref] e Fringe/metropolitan 0.98 [ ].01 \1 million Micropolitan 0.96 [ ] \.0001 Not metropolitan 0.99 [ ].9 or micropolitan Region Northeast 0.81 [ ] \.0001 Midwest 0.96 [ ] \.0001 South 1.01 [ ].5 West 1.00 [ref] e Comorbidity Diabetes mellitus 1.14 [ ] \.0001 Obesity 1.23 [ ] \.0001 CI, Confidence interval; OR, odds ratio. infection, tuberculosis, osteomyelitis, meningitis, necrotizing fasciitis, encephalitis, influenza, septicemia, enterocolitis, endocarditis, urinary tract infection, pneumonia, peritonitis or intestinal abscess, gangrene, appendicitis, MRSA, MSSA, and Pseudomonas infection (Table IV). Impact of serious infections on inpatient mortality Serious infections with increased mortality in comparison to psoriasis patients without serious infections included meningitis (2.60%, 95% CI ), influenza (2.68%, 95% CI ), septicemia (6.30%, 95% CI ), pneumonia (3.40%, 95% CI ), peritonitis or intestinal abscess (4.37%, 95% CI ), MRSA (5.71%, 95% CI ), MSSA (3.33%, 95% CI ), and pseudomonas infection (2.79%, 95% CI ) (Table IV). In multivariate models controlling for sociodemographic factors and serious infections with stepwise selection, only pneumonia (adjusted OR 2.45, 95% CI ), septicemia (adjusted OR 6.71, 95% CI ), enterocolitis (adjusted OR 1.77, 95% CI ), meningitis (adjusted OR 3.91, 95% CI ), encephalitis (adjusted OR 3.58, 95% CI ), and peritonitis/ intestinal abscess (adjusted OR 2.49, 95% CI ) were significantly associated with increased mortality (Table V). DISCUSSION This study demonstrated that serious infections were significantly higher in prevalence for inpatients with psoriasis than for inpatients without psoriasis. Psoriasis was associated with cellulitis, herpes simplex virus infection, fungal infections, infectious arthritis, viral infections, tuberculosis, osteomyelitis, meningitis, encephalitis, septicemia, enterocolitis, MRSA, MSSA, and C difficile infection even after adjusting for demographic factors. The infections associated with highest mortality were pneumonia, septicemia, diverticulitis, enterocolitis, meningitis, encephalitis, and peritonitis or intestinal abscess. The rate of overall serious infections increased over all time intervals examined; when analyzed individually, all serious infections demonstrated increased rates in at least 1 time interval. To our knowledge, previous studies have not examined trends of serious infection in hospitalized patients with psoriasis in the United States. The reasons for these increases are not entirely clear. Previous studies found no increasing trends of serious infections in patients with moderate

6 292 Hsu, Gordon, and Silverberg JAM ACAD DERMATOL AUGUST 2016 Fig 1. Prevalence of serious infections in hospitalized patients. Percent of total hospitalizations versus time intervals ( , , , , ) are plotted for each serious infection in patients with (solid line) and without (dotted line) psoriasis. MRSA, Methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.

7 JAM ACAD DERMATOL VOLUME 75, NUMBER 2 Hsu, Gordon, and Silverberg 293 Table IV. Costs of care, length of stay, and adjusted mortality of patients with psoriasis and serious infections Serious infection Mean cost (SD) Mean length of stay (SD) Adjusted mortality [95% CI] None $11,003 ($96) 4.6 (0.03) 0.74% [ ] Any $13,290 ($166) 6.6 (0.1) 1.78% [ ] Cellulitis $6796 ($88) 4.6 (0.04) 0.18% [ ] HSV infection $10,711 ($982) 6.5 (0.5) 0% Any fungal infection $16,675 ($379) 8.8 (0.1) 1.66% [ ] Infectious arthritis $13,650 ($615) 7.0 (0.4) 0% Viral infection $12,708 ($413) 6.2 (0.2) 1.30% [ ] Tuberculosis $14,928 ($1013) 6.7 (0.5) 0.94% [ ] Osteomyelitis $15,503 ($1078) 9.1 (0.5) 0.21% [ ] Meningitis $20,095 ($1463) 8.2 (0.5) 2.60% [ ] Necrotizing fasciitis $32,915 ($6840) 14.7 (1.6) 0% Encephalitis $20,271 ($1723) 9.1 (0.6) 1.93% [ ] Influenza $11,201 ($836) 5.7 (0.4) 2.68% [ ] Septicemia $22,434 ($451) 9.7 (0.1) 6.30% [ ] Enterocolitis $15,760 ($541) 7.9 (0.2) 2.15% [ ] Pyelonephritis $7583 ($292) 4.0 (0.1) 0% Endocarditis $30,472 ($3259) 10.4 (0.7) 0.57% [ ] Diverticulitis $10,335 ($277) 5.0 (0.1) 0.27% [ ] Urinary tract infection $13,786 ($209) 7.1 (0.1) 1.68% [ ] Pneumonia $16,141 ($266) 7.2 (0.1) 3.40% [ ] Peritonitis/intestinal abscess $24,217 ($1104) 9.5 (0.3) 4.37% [ ] Gangrene $13,563 ($340) 6.7 (0.3) 0% Appendicitis $11,250 ($357) 3.8 (0.2) 0.48% [ ] MRSA $25,039 ($1558) 12.0 (1.3) 5.71% [ ] MSSA $22,449 ($976) 11.4 (0.4) 3.33% [ ] Pseudomonas spp $18,231 ($1783) 8.7 (0.6) 2.79% [ ] Clostridium difficile $10,193 ($374) 6.5 (0.2) 0.42% [ ] CI, Confidence interval; HSV, herpes simplex virus; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; OR, odds ratio. to severe psoriasis who used ustekinumab 17 or adalimumab. 18 However, in the current study, we were not able to determine the history of biologic use. Furthermore, controlling for patients without a diagnosis of psoriatic arthritis did not change the analyses, given that only 4.5% (123) of patients with psoriasis also had a formal diagnosis of psoriatic arthritis. The financial burden of serious infections was substantial in patients with psoriasis. Twenty of 26 serious infections surveyed had higher mean costs of hospitalization and 23 of 26 had higher LOS than that for patients with psoriasis without serious infections. On a national level, psoriasis presents a substantial economic burden 19 and mitigation of infectious complications would dramatically reduce cost. Although we demonstrate that serious infections are on the rise in inpatients with psoriasis, these trends were not only observed in patients with psoriasis. Indeed, several infectious causes increased in patients without psoriasis, suggesting there are other contributory factors in general, such as higher prevalences of diabetes mellitus given increasing prevalences of overweight and obesity. 9 Indeed, presence of obesity or diabetes mellitus were both associated with higher rates of serious infections in patients with psoriasis. The increased rates of serious infections in general and in patients with psoriasis, in particular, is concerning from a public health standpoint. Significant predictors of serious infections in patients with psoriasis included non-white race, lower estimated income quartile, and Medicaid, Medicare, or self-pay insurance status. These findings suggest that poor access to adequate dermatologic care may be associated with higher rates of infections. Issues related to limited access to dermatologic care are becoming increasingly important in an era of narrowing insurance networks and changing health care policies. Indeed, socioeconomic disparities have been observed for rates of hospitalization in psoriasis 20 and other skin diseases, such as pemphigus. 14 Together, these studies highlight the importance of dermatologic care in the treatment of psoriasis and other chronic inflammatory skin disorders for the prevention of infections and other complications. Predictors of inpatient mortality in psoriasis were increasing age, number

8 294 Hsu, Gordon, and Silverberg JAM ACAD DERMATOL AUGUST 2016 Table V. Predictors of mortality in patients with psoriasis Variable Adjusted OR [95% CI] P value Age, y 0-17 Ref e [ ] [ ] [ ] \.0001 $ [ ] \.0001 Insurance Medicare 1.10 [ ].004 Medicaid 1.44 [ ] \.0001 Private insurance Ref e Self-pay 1.79 [ ] \.0001 No charge 1.77 [ ].007 Other 1.09 [ ].3 No. of chronic conditions 0-1 Ref e [ ] \.0001 $ [ ] \.0001 Region Northeast 0.82 [ ] \.0001 Midwest 0.76 [ ] \.0001 South 0.77 [ ] \.0001 West Ref e Serious infection Pneumonia 2.45 [ ] \.0001 Cellulitis 0.22 [ ] \.0001 Septicemia 6.71 [ ] \.0001 Diverticulitis 0.29 [ ] \.0001 Enterocolitis 1.77 [ ] \.0001 Meningitis 3.91 [ ] \.0001 Encephalitis 3.58 [ ] \.0001 Peritonitis/intestinal abscess 2.49 [ ] \.0001 CI, Confidence interval; OR, odds ratio. of chronic conditions, region, insurance type, and several infections, specifically. That insurance typee namely Medicaid, self-pay, and Medicareealso were predictors of mortality further highlights that there are disparities in how well different patients with psoriasis manage their disease. Indeed, patients with undiagnosed psoriasis tend to be non-white, male, less educated, and unmarried 21 ; another study found black race to be associated with increased psoriasis severity, even though whites have the highest rates of psoriasis. 22 Additional studies are necessary to address these patent racial and socioeconomic disparities in patients with psoriasis. Strengths of this study include an analysis of a nationally representative sample of data over a period of 11 years with over 87 million records. Weaknesses of this study include the absence of medication data in the NIS, which precludes an analysis of systemic therapies and/or biologic use, and more specifically, which medications may be predisposing to infection. Furthermore, time of diagnosis of psoriasis and serious infections were not available in the NIS, precluding study of temporal relationships between psoriasis and comorbidities. Lastly, there is potential for selection bias as we analyzed an inpatient database; consequently, serious infections may not be on the rise in all patients with psoriasis, but rather the ones with more severe disease. Nevertheless, this cohort is well suited to study rates of serious infections in psoriasis, because most of the infectious causes examined would require hospitalization for evaluation and management. However, future US population-based studies may be needed to confirm these associations. In conclusion, serious infections are increasing in incidence in inpatients with psoriasis. In addition, patients with psoriasis have higher odds of certain infections, such as tuberculosis, meningitis, and fungal infections. Further research is needed to confirm these findings and understand the mechanisms of these associations to develop large-scale interventions aimed at prevention. REFERENCES 1. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70: Boyman O, Conrad C, Tonel G, Gilliet M, Nestle FO. The pathogenic role of tissue-resident immune cells in psoriasis. Trends Immunol. 2007;28: Gaspari AA. Innate and adaptive immunity and the pathophysiology of psoriasis. J Am Acad Dermatol. 2006;54: S67-S Bos JD, De Rie MA, Teunissen MBM, Piskin G. Psoriasis: dysregulation of innate immunity. Br J Dermatol. 2005;152: Weinberg JM. An overview of infliximab, etanercept, efalizumab, and alefacept as biologic therapy for psoriasis. Clin Ther. 2003;25: Schmitt J, Rosumeck S, Thomaschewski G, Sporbeck B, Haufe E, Nast A. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol. 2014;170: Dommasch ED, Abuabara K, Shin DB, Nguyen J, Troxel AB, Gelfand JM. The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2011;64: Garcia-Doval I, Carretero G, Vanaclocha F, et al. Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: Patients ineligible vs eligible for randomized controlled trials. Arch Dermatol. 2012;148: Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, JAMA. 2003;289: HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality, Rockville, MD.

9 JAM ACAD DERMATOL VOLUME 75, NUMBER 2 Hsu, Gordon, and Silverberg Icen M, Crowson CS, McEvoy MT, Gabriel SE, Maradit Kremers H. Potential misclassification of patients with psoriasis in electronic databases. J Am Acad Dermatol. 2008;59: Asgari MM, Wu JJ, Gelfand JM, et al. Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, Pharmacoepidemiol Drug Saf. 2013;22: Age and Sex Composition in the United States. United States Census Bureau. cps.html Hsu D, Brieva J, Silverberg JI. Costs of Care for Hospitalization for Pemphigus. JAMA Dermatol. February 10, http: //dx.doi.org/ /jamadermatol [Epub ahead of print]. 15. Centers for Disease Control and Prevention NCHS urban-rural classification scheme for counties. cdc.gov/nchs/data_access/urban_rural.htm United States Department of Labor. Consumer price index Papp KA, Griffiths CE, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168: Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: Results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012;66: Brezinski EA, Dhillon JS, Armstrong AW. Economic burden of psoriasis in the united states: A systematic review. JAMA Dermatol. 2015;151: Hsu DY, Brieva J, Silverberg JI. The Inpatient Burden of Psoriasis in the United States. JAmAcadDermatol. 2016;75: Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES J Am Acad Dermatol. 2009;60: Kerr GS, Qaiyumi S, Richards J, et al. Psoriasis and psoriatic arthritis in African-American patientsethe need to measure disease burden. Clin Rheumatol. 2015;34:

10 296 Hsu, Gordon, and Silverberg JAM ACAD DERMATOL AUGUST 2016 Supplemental Fig 1. Differences in least squares means between each time interval ( , , , , ) for each serious infection are plotted for patients with (solid line) and without (dotted line) psoriasis. Post hoc correction was performed with Tukey method; 95% confidence intervals are presented.