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To compare the medical severity of adolescents with eating disorders not otherwise specified (EDNOS) to those with anorexia nervosa (AN) and bulimia nervosa (BN).
Medical records of 1310 females aged 8 through 19 years treated for AN, BN, or EDNOS were retrospectively reviewed. EDNOS patients were subdivided into partial anorexia (pAN) and partial bulimia (pBN) categories if they met all but one DSM-IV criterion for AN or BN, respectively. Primary outcome variables were heart rate, systolic blood pressure, temperature, and QTc interval on electrocardiogram. Additional physiologically significant medical complications were also reviewed.
25.2% had AN, 12.4% BN, and 62.4% had EDNOS. The medical severity of EDNOS patients was intermediate to that of subjects with AN and BN in all primary outcomes. Patients with pAN had significantly higher heart rates, systolic blood pressures, and temperatures than those with AN; patients with pBN did not differ significantly from those with BN in any primary outcome variable; however, subjects with pAN and pBN differed significantly from each other in all outcome variables. Patients with pBN and BN had longer QTc intervals and higher rates of additional medical complications reported at presentation than other groups.
EDNOS is a medically heterogeneous category with serious physiologic sequelae in children and adolescents. Broadening AN and BN criteria in pediatric patients to include pAN and pBN patients may prove to be clinically useful.
According to current diagnostic criteria, most pediatric patients with disordered eating are diagnosed with eating disorders not otherwise specified (EDNOS), defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as “disorders of eating that do not meet the criteria for any specific Eating Disorder,” a categorization that has long troubled practitioners.[2–9] While a handful of studies have examined bone density, fracture rates, or electrocardiograms in EDNOS patients[10–12], most studies on medical sequelae of disordered eating have focused on bulimia nervosa (BN) or anorexia nervosa (AN), and little work has documented the severity, frequency, or clinical significance of EDNOS in young people.[4, 8, 13–15]
Recent studies of EDNOS patients have focused on psychiatric features, comparing adult patients with partial AN (pAN) or partial BN (pBN) to patients meeting full DSM-IV criteria. Patients with pAN and pBN typically have similar psychological profiles to those meeting full criteria for AN and BN, while pAN and pBN differ significantly from each other despite both being subgroups of EDNOS. [4, 16–30]
Numerous medical organizations including the American Academy of Pediatrics agree that patients with severe malnutrition, bradycardia, hypotension, hypothermia, and orthostasis are critically ill and require hospitalization.[31–32] No study has examined how DSM-IV diagnostic criteria correlate with medical severity, and there are no data to validate the commonly held tenet that EDNOS is associated with lower medical severity.
This paper will review current diagnostic criteria and discuss their utility in predicting the medical severity of patients with eating disorders (EDs). Our goal is to describe a large group of pediatric EDNOS patients and compare them to pediatric AN and BN patients. In addition, we will compare the medical severity of EDNOS adolescents with pAN or pBN to those meeting full diagnostic criteria. We predicted that those with EDNOS and pAN or pBN would be less medically compromised than those with full DSM-IV syndromes. Furthermore, we predicted that pAN and pBN would differ significantly from one other with respect to meeting hospitalization criteria.
All 1310 female patients aged 8–19 years diagnosed with AN, BN, or EDNOS in an academic pediatric ED program from January 1997 through April 2008 were identified. All subjects were initially clinically diagnosed by a board-certified psychiatrist or psychologist with expertise in the assessment of children and adolescents with ED, after diagnostic interviews with both patients and parents or guardians, and as part of a comprehensive evaluation by a multidisciplinary team. Both inpatients and outpatients were included. Because of small within-gender cell sizes that prevented adequate assessment of potential gender differences, male patients were excluded from analyses, as were patients found not to have a DSM-IV diagnosable ED during their evaluation or treatment. A waiver of informed consent and a HIPAA-compliant waiver of individual authorization were granted; all data collection protocols were approved by our Panel on Medical Research in Human Subjects and compliant with the Health Insurance Portability and Accountability Act of 1996.
DSM-IV criteria for EDs are guidelines, and allow for latitude in their application in clinical settings. However, this study was designed to answer a primary research question of how DSM-IV diagnostic criteria predict medical outcomes; hence, a systematic retrospective review of all medical records was conducted by two independent assessors and reviewed by the primary investigator, to note relevant clinical parameters at presentation. When indicated after this comprehensive review, patients were recategorized from their original clinical ED diagnosis, using strict DSM-IV criteria (Figure 1). In premenarchal females, AN was diagnosed if weight and psychiatric criteria were met as per DSM-IV guidelines.
Predictor variables for primary analyses were categorical diagnoses of EDNOS, AN, and BN. To examine each separate criterion for AN and BN in the DSM-IV, patients with EDNOS were further divided into non-overlapping pAN and pBN categories:
Medical outcome variables were defined in Table 1, based on national guidelines for acute hospitalization in ED adolescents.[2, 32, 34] Primary outcomes were heart rate, blood pressure, temperature and QTc interval. Severe malnutrition was not a primary outcome in this study as pAN and pBN categories were partly defined by weight. Secondary outcome variables included rates of admission within two weeks of presentation, length of disease, complications attributed to the ED occurring prior to presentation, and complications occurring during the first hospital stay, if the hospitalization occurred within 2 weeks of presentation. There were no deaths in this series during the first hospital stay.
Heart rates (measured manually) and blood pressures (using a sphygmomanometer) were taken after lying supine for 5 minutes, and standing heart rate and blood pressure were taken after standing for two minutes. If heart rates or blood pressures were low supine, or if significant dizziness was reported, standing vital signs were not obtained. Temperatures were obtained orally using a digital thermometer. Electrocardiograms were performed by trained staff members using a standard 12-lead method. Weights were recorded in gowns with no clothing, and heights obtained using a stadiometer. As electrocardiograms and labs were performed clinically rather than as part of a research protocol, the majority but not all patients had these tests performed (see Table 2).
Body mass index (BMI) was calculated using the equation: BMI = weight in kilos/(height in meters)2. BW was calculated using gender-specific 2000 CDC BMI-for-age growth charts for children and adolescents aged 2–20 years (http://www.cdc.gov/growthcharts). The 50th percentile BMI for exact age at presentation on the CDC chart was used to calculate an MBW, together with the height at presentation.
Reported maximum weights were extracted from the medical record. Total weight loss prior to presentation was defined as the maximum weight minus the weight at presentation. Total percentage weight loss was defined as the total weight loss divided by the maximum weight, multiplied by 100. The rate of weight loss was defined as total percentage weight loss divided by the months from the date of maximum weight to the date of presentation. If the maximum weight was the weight at presentation, the total weight loss was zero, as was the rate of weight loss.
Data were described with standard mean and frequency statistics, and analyzed using chi-squared testing, Student's t-testing, and ANOVA with Tukey's post-hoc comparisons testing on SPSS v17.0 software. In order to guard against Type I error in analysis of the primary aims, a Hochberg modified Bonferroni procedure was employed. To further assess relationships between primary predictor and outcome variables, age and length of disease were added as covariates using ANCOVA.
Demographic and clinical characteristics are presented in Table 2. Table 3 outlines medical differences between DSM-IV ED categories at presentation. The medical severity of EDNOS patients fell between that of subjects with AN and BN in most criteria examined. Differences were statistically significant for all primary outcomes. Pediatric patients with EDNOS had similar age, length of disease, and rate of weight loss as those with AN, but otherwise post hoc testing revealed that most differences in secondary outcomes were significant between all three diagnostic categories.
Medical outcomes were compared between subjects with pAN and AN, pBN and BN, and pAN with pBN (Table 4). Patients with pAN did not differ from those with AN in sexual maturity rating (SMR), but patients with pBN were slightly less pubertally mature than their BN counterparts (SMR breast 4.5 vs. 4.7, t=2.6, p<.05; pubic hair 4.5 vs. 4.7, t=2.8, p<.01). All differences noted in primary analyses detailed in Tables 3 and and44 retained significance after the Hochberg modified Bonferroni correction was applied, except for those related to temperature differences between pBN and BN patients. Of note, all relationships between primary predictor and outcome variables remained significant after controlling for age and months of disease.
In exploratory analyses, pAN subgroups were compared to AN and pBN subgroups to BN. Partial AN-Low Weight/Menstruating patients were significantly older, while those not meeting psychiatric criteria were the youngest (15.8 years vs. 14.3: pAN-Low Weight/Not Menstruating, 14.8: pAN-Less than 90%, 15.0: pAN-25%, and 15.3: AN, F=9.7, p<.001). Partial AN-Low Weight/Not Menstruating patients had the longest QTc intervals (394 vs 393: pAN-Low weight/Menstruating, 386: pAN-Less than 90%, 378: pAN-25%, F=3.0, p<.05), The pAN-25% group, despite being nearly at their MBW (97.7% MBW vs. 77.7: pAN-Low weight/Menstruating, 75.7: pAN-Low Weight/Not Menstruating, 87.2: pAN-Less than 90%, and 75.8: AN, F=198.8, p<.001), demonstrated the highest percentage of weight lost (34.0 vs. 19.6, 16.6, 19.2, and 23.0, F=32.9, p<.001) at the fastest rate (3.5%/month vs. 2.6, 2.8, 2.4, and 2.4, F=3.9, p≤.005). They also had higher rates of bradycardia (43.5% vs. 22.5, 28.5, 28.9, and 38.5, χ2=14.4, p<.01) and orthostasis by heart rate (57.1% vs., 52.7, 37.0, 32.4, and 32.8, χ2=18.0, p≤.001) than all other pAN subgroups. Patients in the pAN-Less than 90% group were more likely than all except AN to meet any admission criteria, excluding weight (76.1% vs. 66.7, 61.5, 59.5, and 73.0, χ2=11.8, p<.05). Patients with AN were most likely to be hypotensive (16.2% vs. 2.7: pAN-Low weight/Menstruating, 6.9: pAN-Low weight/Not Menstruating, 5.0: pAN-Less than 90%, and 6.5: pAN-25%, χ2=26.6, p<.001), and had the lowest phosphorus levels (3.7 vs. 3.9, 4.0, 3.9, and 3.8, F=3.7, p≤.005). There were no differences noted among pAN subgroups and AN with regards to rates of hypothermia, orthostatic hypotension, hypokalemia, serious hospital complications or in complications prior to presentation.
Most pBN subgroups did not show significant differences from each other in medical hospitalization criteria, although small cell sizes precluded meaningful analyses of some categorical outcomes. Patients with BN were older (16.4 years vs. 15.8: pBN-Binge/Purge, 15.6: pBN-Purge only, and 15.6: pBN-Binge only, F=6.4, p<.001) and had disease longer than all pBN subgroups (26.6 months vs. 19.4, 16.5, and 18.7, F=8.5, p<.001). Partial BN-Purge only patients had lost weight faster than BN patients (2.4 % month vs. 1.5: pBN-Binge/Purge, 1.9: pBN-Binge Only, and 1.4: BN, F=3.0, p<.05). There were no differences between groups in mean percentage weight loss, blood pressure, orthostatic changes, potassium and phosphorus levels, length of stay if hospitalized, and complication rates.
These analyses reveal that in this adolescent ED population, 62.4% are properly diagnosed with EDNOS, if strictly applying current DSM-IV standards. However, 61.6% of these EDNOS patients meet recommended criteria for medical hospitalization, and are more compromised than BN patients in most medical outcomes. Despite their younger age, they displayed similar disease duration and rates of weight loss, QTc prolongation, orthostasis, and hypokalemia as their full diagnostic counterparts. This is despite the fact that they weighed significantly more than patients with AN. These results do not support our initial hypothesis that EDNOS would be less medically severe than AN or BN.
We proposed new groupings of pAN and pBN patients within the EDNOS group, with each subgroup directly challenging one DSM-IV criterion for AN or BN. When pAN patients were compared to those with AN, there were few differences. pAN patients as a whole were less likely to have a low heart rate or blood pressure, but did not differ from AN patients on most other medical outcomes. Adolescents with pAN were younger and weighed significantly more, but had lost weight more rapidly than those with AN and had a shorter disease duration.
Of pAN subgroups, those EDNOS patients who had lost over 25% of their pre-morbid body weight (pAN-25) appeared more compromised than other subgroups of pAN, and even more than AN patients in some medical outcomes. This is the case despite being at a significantly higher, near “ideal” body weight, reminding us that malnutrition is a complex disease with manifestations at multiple weights. In addition, another pAN subgroup, those not meeting menstrual criteria (pAN-NM), was older, possibly indicating later recognition of the ED.
Patients with pBN were younger, had a shorter duration of disease, weighed less and had lost weight more rapidly than their BN counterparts. However, pBN patients and subgroups did not differ significantly from BN adolescents on most other medical outcomes examined.
When pAN was compared to pBN, pAN patients were more medically severe, with the exception of duration of illness and the QTc interval, where pBN patients had more months of disease and longer QTc intervals. This mirrors our comparison of BN to AN, where BN patients report nearly twice the duration of disease and longer mean QTc intervals. Patients with pAN and pBN were similar only in rates of hypokalemia, hypophosphatemia, and orthostasis. This lends credence to the idea that EDNOS is too heterogeneous a category, as patients diagnosed differ more from each other than they do from AN and BN, respectively. EDNOS patients who narrowly miss criteria for AN and BN are often medically compromised and in need of treatment.
To our knowledge, this is the first published comparison of reported complications among ED adolescents from all DSM-IV diagnostic groups. While AN patients certainly had a high rate of objective medical complications observed during their first hospital stays, the complication profiles of other patients was hardly reassuring. Partial AN and pBN patients also displayed high rates of hospital complications at around 18% and 19% respectively, and BN and pBN patients reported significantly higher numbers of serious complications prior to presentation than their AN and pAN peers. While further prospective study is required to confirm these findings, they imply the need to better delineate predictors of complications and medical protocols in each DSM group separately, rather than measuring each group against an AN standard.
Limitations of this study include that it is a clinical sample from a subspecialty ED program, which limits its generalizability. It is also an exclusively female sample, and while it is critical that we better learn how to manage adolescent males with EDs, this study does not inform that pursuit. Data were collected retrospectively, and thus data may be missing for non-random reasons not yet identified. In addition, clinical decisions had been made which influenced the choice of laboratory tests, which may have introduced bias based on medical severity. In general, most variables were missing fewer than 10% of data, but phosphorus levels, electrocardiograms, and orthostatic testing were missing in 10–20% of subjects, thereby necessitating caution in the interpretation of these variables.
A limitation of any study of current medical hospitalization criteria for ED patients is that they were derived from expert consensus and not from longitudinal study. Bradycardia, hypotension, orthostasis, and hypothermia have clearly been shown in studies to be strong indicators of a malnourished state, and have therefore been adopted as indicators of medical severity in patients with EDs.[31–32] In addition, QTc prolongation has been shown to be a risk factor for sudden cardiac death, which makes it the most concerning complication of the ones examined here. However, we do not have evidence that these findings mandate hospitalization, nor are we certain that hospitalization improves long-term medical outcomes. It is possible that in the future outpatient treatment regimens may prove to be equally effective and safe in treating these cardiac sequelae, and further prospective study is urgently needed to delineate the most appropriate type of interventions, and when they are indicated.
These analyses reveal that there exist adolescent ED patients within a larger EDNOS group who are medically similar to AN and BN patients. They provide a rationale to consider changes to the diagnostic criteria for adolescents with ED, as other authors have recently proposed.[3–4, 6, 9, 15–16, 25–26, 37–46] For example, cut-points of weights, duration of behaviors and endocrine dysfunction are not currently evidence-based and thus may not be truly reflective of medical severity. Our study also suggests that current criteria for medical intervention may be most appropriate for adolescents with AN, but that we may miss critical opportunities for intervention and prevention in other ED groups.
Finally, our data propose another possibility of diagnostic groupings, which are shown in Figure 2, illustrating the original percentage of patients in AN, BN, and EDNOS categories, and comparing that with a new grouping where pAN and pBN are counted as a subgroup of AN and BN, respectively. If patients with pAN and pBN are combined into AN and BN groups, only 14.3% of patients with “true” EDNOS remain, similar to another recent diagnostic reclassification of adult ED patients. If over 60% of patients have EDNOS by DSM-IV criteria, they are effectively forced into diagnostic categories lacking definition, health care coverage, or medical knowledge. In adolescents and children especially, eating disorders are a devastating set of diseases with multiple long-term sequelae. It is clear that a diagnosis of EDNOS does not imply a reassuring medical profile, and these findings underscore the need to intervene early, even when young patients do not meet full diagnostic criteria for AN or BN. Future studies should be directed toward better defining the best clinical criteria by which we can intervene both medically and psychiatrically in these diverse set of illnesses.
We would like to gratefully acknowledge Dr. Iris Litt for her support and help with editing of this manuscript, and all of the research assistants at the Stanford WEIGHT lab who have assisted with data collection for this study.
Funding disclosure: The project was funded in part by the Stanford Pediatric Research Fund, Jenny Wilson received funding from the Stanford Medical Scholars Research Program, and Dr. Lock received funding from NIH K24 MH074467.
Conflict of interest: Dr. Peebles, Dr. Hardy, Jenny Wilson, and Dr. Lock have no financial or personal relationships that could lead to conflict of interest.
Clinical trial disclosure: This article does not report the results of a clinical trial.