Inpatient burden of juvenile dermatomyositis among children in the United States

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by proximal muscle weakness concurrent with specific cutaneous manifestations. [1] In the United States, JDM has an estimated incidence of 2–4 per million children per year. [2] While improved management of the disease has led to reduced mortality in recent years, up to 40% JDM patients continue to have active disease despite treatment. [3, 4] Ongoing disease activity, cumulative damage, and aggressive immunosuppressive treatments remain a concern for long term outcomes and quality of life. [4] Previous studies have compared cost of specific JDM treatment regimens [5], evaluated the inpatient burden of adult dermatomyositis [6], and examined economic burden of other childhood inflammatory conditions such as JIA [7]. However, little is known about the inpatient burden of JDM in the United States. As a result, use of a comprehensive, national inpatient database could help to elucidate the economic burden posed by JDM.

Previous studies found racial/ethnic and socioeconomic differences in hospitalization rates and outcomes for stroke [8], cardiovascular disease [9], asthma [10], acute respiratory illness [11], pemphigus [12], and adult dermatomyositis [6]. We hypothesized that JDM is also associated with similar racial/ethnic and socioeconomic differences, possibly related to lack of insurance coverage and reduced access to specialty care, such as rheumatology and dermatology. In the present study, we analyzed the prevalence and predictors of hospitalization, cost of care and length of stay in US patients with JDM.

The present study finds that JDM incurs a significant inpatient burden, with primary diagnoses having a higher cost of care (approximately $3000 more per hospitalization) and secondary diagnoses having longer hospitalizations and cost of care (also approximately $3000 more per hospitalization) compared to no diagnosis of JDM. The higher cost of care is likely related to additional workup required for diagnosis, disease comorbidity and treatment regimen required for the disease. Previous studies have suggested that infection may play a role in both the development [18] and recurrence [19, 20] of JDM episodes. In our study, we found increased rates of infection i.e. cellulitis among JDM patients. Multiple mechanisms may make individuals with JDM more prone to infection with pathogens such as staphylococcus. Skin breakdown, seen in JDM patients with calcinosis and cutaneous ulceration, may serve as a nidus for infection. In addition, underlying immune dysregulation such as granulocyte chemotactic defects may contribute to infection risk. [21] The long-term use of immunosuppressants (e.g. corticosteroids, methotrexate) likely also contributes to infection risk. A novel finding that ‘other arthropod-borne diseases’ represented the 5th most common primary diagnosis among patients with a secondary diagnosis of JDM (Table 2) deserves further study to determine the strength of this association, whether the code refers specifically to arthropod-borne diseases per se versus chief complaints (e.g. cutaneous eruptions, other infections) for which arthropod-borne diseases are on the differential diagnosis, or an outlier due to readmission of a few inpatients with JDM who happened to have had arthropod-borne diseases. JDM patients within our study were also shown to have higher rates of comorbid chronic conditions. Emerging literature supports the finding that JDM patients are often medically complex. For example, we recently found in a separate study that inpatients with JDM had increased odds of multiple cardiovascular and cerebrovascular comorbidities. [22] It is likely that sequelae of JDM itself, adverse effects of treatment (e.g. infections, side effects of steroids), and concomitant autoimmunity contribute to higher chronic condition counts in JDM, with further study needed to better clarify the exact comorbidities in this population. In addition, while current treatment regimens favoring rapid and aggressive management, such as those involving high-dose intravenous pulse methylprednisone therapy, improve outcomes and prognosis of the disease [23], they may also contribute to inpatient costs. Unfortunately, we did not have access to specific diagnostic tests and medications used during hospitalizations, as these were not recorded within the NIS. As a result, future studies are needed to determine specific contributors to inpatient costs. Notably, annual prevalence for both primary and secondary diagnoses have not increased over time as opposed to trends seen in adult dermatomyositis. [6] Future studies are needed to assess whether disease pathophysiology or management may explain the differences in these trends.

There were significant age, sex, seasonal, financial, and regional differences in hospitalization for JDM. In particular, higher rates of hospitalization were found in JDM patients who were older, female, received non-Medicaid government administered insurance coverage (e.g. KidCare, CHIP, other federal/state/local government programs), hospitalized in metropolitan areas, and hospitalized in non-winter seasons when compared to the control group. Hospitalization rates were highest for the 6–11 year old age group, which corresponds to the average age of onset (approximately 7 years) found in other studies. [18, 24] Higher rates of hospitalization in females are likely related to females having higher overall disease prevalence. [2, 18] Hospitalizations for JDM were more likely to occur in non-winter seasons, which stand in stark contrast to the higher frequency of winter admissions seen in control patients. This finding reinforces that ultraviolet light and other environmental exposures may play a role in disease pathogenesis and exacerbation, which corroborates the view that JDM can be a photosensitive condition [25‐27] and that JDM patients should be advised to routinely use sunscreen. [28]

Financial coverage and regional differences in hospitalizations may point to differences in access to care for different patient populations. Notably, patients were more likely to be hospitalized if they were covered under government programs, excluding Medicaid. These alternative programs often represent efforts at the state/local level to provide assistance for children of lower income families. As a result, increased risk of hospitalization for patients with these alternative forms of coverage may represent the decreased access to care that lower income families face. Paradoxically, hospitalizations rates were lower among JDM patients with Medicaid coverage. As a result, further research is needed to evaluate how differences in group characteristics and social determinants of health between those covered under different government programs may contribute to differences in outcomes as seen in this study. Additionally, the majority of hospitalizations occurred in metropolitan locations. This speaks to multiple potential issues, including access to outpatient care in urban settings and lack of pediatric rheumatologists in more rural settings requiring treatment at large referral centers in urban areas, both of which may be attributable to a limited supply of pediatric rheumatologists [29] and pediatric subspecialists in general. [30] This is further reinforced by the fact that hospitalizations for JDM in micropolitan locations resulted in an 80% longer LOS compared to metropolitan locations. Further research is needed to evaluate how distribution and access to the pediatric rheumatology workforce affects patient outcomes.

Interestingly, race/ethnicity did not play a major role in increased hospitalizations, contrasting trends seen across other diseases, including adult dermatomyositis [6], pemphigus [12], and psoriasis [31] where racial/ethnic differences did affect rates of hospitalization. However, race was an important contributor to inpatient burden in terms of both length of stay and cost, with Hispanic patients having an estimated 32% longer hospitalization and 35% higher cost of care and other non-white racial groups (excluding Black and Hispanic patients) having 80% longer hospitalizations. These differences in length of stay and costs of care may point to differences in disease manifestations or severity among different races/ethnicities. Indeed, previous studies have found differences in human leukocyte antigen (HLA) frequencies among different ethnic groups, with the HLA-DQA1*0501 allele having a high frequency in Hispanic JDM patients. [32] In addition, studies have suggested that differences between patient HLA subtype and autoantibody associations may help predict disease subtype and severity. [33] Alternatively, access to care may be contributing to racial/ethnic differences. However, one study, which found that minority race and lower family income were associated with worse outcomes—as measured by Childhood Health Assessment Questionnaire, patient global scores, and health-related quality of life scores—did not find associations between race and proxy measures of access to care e.g. time to diagnosis, disease duration, and treatment. [34] In our own study, we did not find that Black patients experienced a difference in hospitalization, length of stay, or cost of care, although we did find that these outcomes differed among other minority groups. Further research examining the relationship of race/ethnicity to outcomes in JDM are warranted.

Strengths of this study include an analysis of a nationally representative sample of all payer data over a period of 11 years with over 14 million pediatric records. JDM patients were identified using the previously validated ICD-9-CM codes for dermatomyositis in the inpatient setting. [13] Limitations of this study include the inability to distinguish between different degrees of disease severity or specific clinical features. This limited our ability to examine how differences between individual hospitals and patient characteristics might contribute to LOS and cost of care. Due to the structure of the NIS dataset, it was not possible to determine how many of the hospitalizations were due to readmissions or transfers between hospitals. In addition, cost analysis did not include costs of physician services, out-of-pocket expenses or outpatient costs. Thus the total economic burden of JDM is likely much higher. In addition, while common symptoms for JDM were higher among the JDM cohort, little additional insight could be gleaned due to lack of symptom coding within the database, as prevalence of these codes was much lower than documented prevalence of these symptoms. [16, 17] There was a large frequency of missing data for season, race/ethnicity, and hospital location in NIS. However, there were no significant differences of missing values between hospitalizations with a primary, secondary or no diagnosis of dermatomyositis. Finally, geographic variation was considered by four Health Resources and Services Administration regions. Controlling for region did not attenuate the observed seasonal, racial/ethnic, or hospital location differences. However, future studies using more granular distinctions of geographic location would be useful to further validate these seasonal, racial, and hospital location differences.

The findings of this study indicate that the inpatient burden of JDM is extensive. Cost was higher for patients with primary JDM while both length of stay and cost were higher for secondary dermatomyositis versus those without. Older age, female sex, non-winter season, non-Medicaid administered government insurance coverage, and metropolitan area were associated with higher rates of hospitalization for JDM while race/ethnicity was more influential in resulting in increased LOS and cost of care, particularly in Hispanic populations. Future research is needed to identify how factors such as access to care may relate to the financial, regional, and racial differences found within this study.