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Disordered eating and food restrictions in children with pandas/pans

JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume xx, Number x, 20xxª Mary Ann Liebert, Inc.
Pp. 1–9DOI: 10.1089/cap.2014.0063 Disordered Eating and Food Restrictions in Children with PANDAS/PANS Megan D. Toufexis, DO,1 Rebecca Hommer, MD,2 Diana M. Gerardi, MA,1 Paul Grant, MD,2 Leah Rothschild, BA,2 Precilla D'Souza, NP,2 Kyle Williams, MD,3,4 James Leckman, MD, PhD,5 Susan E. Swedo, MD,2 and Tanya K. Murphy, MD, MS1,6 Objective: Sudden onset clinically significant eating restrictions are a defining feature of the clinical presentation of some ofthe cases of pediatric acute-onset neuropsychiatric syndrome (PANS). Restrictions in food intake are typically fueled bycontamination fears; fears of choking, vomiting, or swallowing; and/or sensory issues, such as texture, taste, or olfactoryconcerns. However, body image distortions may also be present. We investigate the clinical presentation of PANS disorderedeating and compare it with that of other eating disorders.
Methods: We describe 29 patients who met diagnostic criteria for PANS. Most also exhibited evidence that the symptomsmight be sequelae of infections with Group A streptococcal bacteria (the pediatric autoimmune neuropsychiatric disorderassociated with streptococcal infections [PANDAS] subgroup of PANS).
Results: The clinical presentations are remarkable for a male predominance (2:1 M:F), young age of the affected children(mean = 9 years; range 5–12 years), acuity of symptom onset, and comorbid neuropsychiatric symptoms.
Conclusions: The food refusal associated with PANS is compared with symptoms listed for the new Diagnostic andStatistical Manual of Mental Disorders, 5th ed. (DSM-V) diagnosis of avoidant/restrictive food intake disorder (ARFID).
Treatment implications are discussed, as well as directions for further research.
growing body of literature documenting that viral and bacterialinfections can precipitate acute-onset food restriction (Patton et al.
In addition to the sudden overnight onset of classic 1986; Park et al. 1995; Sokol and Gray 1997; Simon 1998; Sokol obsessive-compulsive symptoms, the sudden onset of reduced 2000, Watkins et al. 2001; Storch et al. 2004; Calkin and Carandang and restricted food intake is one of the defining diagnostic symptoms 2007). Systemic diseases, including autoimmune disorders such as of pediatric acute-onset neuropsychiatric syndrome (PANS) (Swedo systemic lupus erythematosus (Toulany et al. 2014), have also been et al. 2012). Multiple etiologies for PANS have been hypothesized, reported to cause food restrictions via immune dysregulation. An- ranging from genetic and immunologic disorders to postinfectious orexia nervosa (AN) has also been postulated to result when dis- sequelae. When the symptoms are preceded by a group A strepto- ease-related loss of appetite produces excessive weight loss (Dally coccal (GAS) infection, the condition is referred to as ‘‘pediatric 1969; Beumont et al. 1978) and subsequent development of body autoimmune neuropsychiatric disorder associated with streptococcal image distortions.
infections'' (PANDAS) (Swedo et al. 1998). In 1997, Sokol and In youth with PANDAS, food restriction has been reported to Gray described the first cases of ‘‘PANDAS anorexia'' (PANDAS- occur in the context of obsessional fears about contamination, as AN) in their eating disorders unit at the Menninger clinic (Sokol well as in the context of the sudden onset of fears of swallowing, and Gray 1997). Notably, the PANDAS-AN patients described choking, or vomiting that are often associated with sensory phe- were prepubescent, feared weight gain as a result of body dys- nomena (e.g., the perceived texture or appearance of the food). In morphic issues, and exhibited symptoms temporally related to a rare instances, these fears lead to the child's refusal to ingest GAS infection. Additional reports document positive GAS cultures anything orally including any liquids. Contamination fears may among youth with abrupt onset of choking fears and refusal to lead to dietary restriction of all or selected food items (Bernstein swallow (Henry et al. 1999). These observations contribute to a et al. 2010). For example, a child with PANDAS was reported to 1Division of Pediatric Neuropsychiatry, Rothman Center, Department of Pediatrics, University of South Florida, St. Petersburg, Florida.
2Pediatrics & Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland.
3Pediatric Neuropsychiatry and Immunology Clinic, Massachusetts General Hospital, Boston, Massachusetts.
4Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
5Child Study Center, Yale University School of Medicine, New Haven, Connecticut.
6Department of Psychiatry, University of South Florida, Tampa, Florida.
This research was supported (in part) by the Intramural Research Program of the NIMH, including protocol 11-M-0058 (NCT01281969).
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have a fear of choking and contamination that led to complete children had tics, with an average YGTSS = 16.6 ( – 7.9 SD) (see cessation of food consumption and loss of 10% of the subject's Table 1). Two thirds (n = 19) of the children (66%) reported that body weight (Storch et al. 2004). Another report detailed the abrupt their food restrictions were secondary to contamination fears (see onset of obsessions about choking, accompanied by refusal to Table 2). Of those with contamination fears, 12 had fears involving swallow, in association with a positive GAS culture (Henry et al.
germs, three had fears involving poison, and one each had fears of 1999). Restricted eating also has been reported to occur secondary allergens, bleach, illicit drugs, or ‘‘the essence and personality of to new onset of body image distortions of being ‘‘too fat'' or not other people.'' Others expressed fears of vomiting (28%, n = 8) or having a ‘‘six-pack'' (Swedo et al. 2012). To date, little has been choking (21%, n = 6). In addition to food restriction, five patients published on food restrictions in PANS. We report experience with (17.2%) refused to swallow their own saliva, and another five re- 29 patients who met criteria for PANS and who also exhibited fused all food for several days or longer. Three children (10%) acute-onset food restriction.
expressed concerns about weight or body shape. Mean change inweight (in pounds) was - 4.21 ( – 5.85 SD) and mean percent body weight change was - 4.89% (1.91 kg – - 2.66 SD). In the USFsample, 12 out of 13 cases, and in the NIMH sample 14 out of 16 The patients described in this series were participants in clinical cases, had generalized OCD in addition to food restriction. Mean trials at the National Institute of Mental Health (NIMH) or at the illness duration was 2.68 months ( – 1.68 SD). For PANS neuro- Rothman Center of Neuropsychiatry at the University of South psychiatric symptoms, see Table 3.
Florida (USF). All subjects met criteria for PANDAS or PANS and Eighteen children (62%) were confirmed to have had a positive reported new, abrupt onset of eating restrictions or food avoidance.
rapid GAS test or culture at or near the time of PANS onset Children participating in the NIMH trial (n = 16) were among a (See Table 1). Six youth had been exposed to GAS. Mycoplasma larger cohort enrolled in a study of intravenous immunoglobulin pneumonia (MP) exposure or infection was evident in 4 of 12 (IVIG) for the treatment of PANDAS (NCT01281969). This study children examined, 3 of whom (all male) had positive MP immu- was approved by the National Institutes of Health (NIH) Central noglobulin (Ig) G and negative MP IgM, and 1 of whom (female) Nervous System (CNS) institutional review board (IRB); parents had positive MP IgG and IgM. A few children had more than one provided informed consent and children provided assent for study reported infectious trigger.
participation. Children included from USF (n = 13) were fromthree studies, with most from a larger cohort of participants in astudy investigating azithromycin as a PANS treatment (n = 10; NCT01617083, 6119-128500). These studies were approved by the Patient 8 was an 8-year-old male who presented to USF-affiliated IRB; parents provided informed consent and chil- USF 1 month following the sudden onset of severe acute-onset dren provided assent for study participation. All of the patients met contamination fears, food refusal, and tics. Past medical history was full criteria for PANS; some also had evidence of preceding GAS significant for a viral infection (gastrointestinal [GI] symptoms) infections and, therefore, met criteria for PANDAS. Pertinent immediately preceding the PANS symptoms, and a lifetime history subject data are summarized in Table 1.
of frequent GAS infections leading to adenotonsillectomy. Pre-morbid psychiatric history was notable for attention-deficit/ hy- peractivity disorder (ADHD) and minor separation anxiety disorder Symptom severity was measured using the Children's Yale- (SAD). Physical examination was only remarkable for moderate Brown Obsessive Compulsive Scale (CY-BOCS) (Scahill et al.
livedo reticularis. The patient started having fears of dying sud- 1997) and Yale Global Tic Severity Scale (YGTSS) (Leckman denly while he and his family were at a restaurant. He thought he et al. 1989). All assessments were conducted or reviewed by trained was having an allergic reaction, and despite efforts to assuage his clinicians with experience in pediatric obsessive-compulsive dis- anxiety, he began having a panic attack. Although he had no history order (OCD) and tic disorders. Comorbidity symptoms were col- of food allergies, he then developed contamination fears related to lected at both sites using PANS/PANDAS checklists as well as allergens in food, and he refused to eat most solid food. His mother symptoms deemed present in the clinical evaluation.
reported that when she attempted to give him dry toast, he refused Laboratory tests for streptococcal infection included anti-DNase to eat it and began to dry heave. In addition to allergens, he ex- B and antistreptolysin O (ASO) titers. Because of differences in pressed concern that ‘‘other people's medications'' were in his laboratory standardization, thresholds of elevation differed be- food. At evaluation 1 month post-onset, the parents reported that tween sites. Thresholds used to designate groups into elevated or the child had lost 2 lb (3% of his body weight). All laboratory unelevated categories at each site were as follows: ASO > 160 IU/mL values were within normal limits, including streptococcal and for ages 0–6 and > 200 IU/mL for ages 7–17 (USF); ages 5–17 mycoplasma titers. Out of a desperate desire to get him to eat, his years > 640 IU/mL (NIMH); anti-DNase B > 60 U/mL for ages 0–6 mother began giving him fake allergy pills (i.e., Sweet Tarts), so and > 170 U/mL for ages 7–17 (USF); > 375 U/mL (NIMH). As- that he would eat more. However, this measure soon failed, and the says were performed by the USF clinical research laboratory, or boy's contamination fears generalized to the point where his intake for NIMH subjects, Mayo Medical Laboratories in Rochester, was limited to clear liquids. He was started on azithryomycin treatment and, within 1 month, his worries about allergens andmedication poisoning were near remission, and he was eating anddrinking normally.
Twenty-nine children are the subjects of this report, including 20 Patient 12 was a 10-year-old male with a past males (69%) and nine females (31%), with mean age of 9 years history of ADHD, who presented at NIH with sudden-onset severe (range 5–12 years). All children reported obsessive-compulsive OCD and a specific fear that his hands and lips were contaminated symptoms, with an average CY-BOCS = 30.1 ( – 5.2 SD). Eighteen with bleach cleaner. He had tested positive for GAS and had been DISORDERED EATING IN PANDAS/PANS Table 1. Patient Demographics, Premorbid History, Baseline Scores, and Laboratory Results History of infection Exposure to viral Frequent staphylococcal Exposure to virus (rapid antigendetection negative) Infantile febrile seizures Speech delayTics (mild) Frequent otitis mediaPE tubes Frequent otitis mediaPE tubes Borderline adrenal suppression(secondary to inhaledcorticosteroids) Frequent otitis media (rapid antigendetection negative) (rapid antigendetection negative) (rapid antigendetection negative) TOUFEXIS ET AL.
Table 1. (Continued) History of infection Confirmed Influenza Frequent otitis mediaT&ATics with EBV Frequent otitis media CYBOCS, Children's Yale-Brown Obsessive Compulsive Scale; YGTSS, Yale Global Tic Severity Scale; ASO, antistreptolysin O; SAD, separation anxiety disorder; T&A, tonsil and adenoid surgery; GAD, generalized anxiety disorder; URI, upper respiratory infection; ADHD, attention-deficit/hyperactivity disorder; PE, pressure equalizer, GERD, gastroesophageal reflux disease; EBV, Epstein–Barr virus.
exposed to siblings who tested positive for GAS prior to his sudden constantly apologized and expressed guilt about supposed trans- onset of symptoms. The GAS infection was treated with a 5 day gressions and would hit herself on the head or engage in other self- course of azithromycin. After the children's GAS infections, their mother cleaned the house with bleach, and shortly afterwards, the At the time of presentation to NIH, the child's overscrupulosity patient developed an obsession that any food he touched would had escalated to the point that she felt she ‘‘did not deserve to eat'' become contaminated with bleach, harming or killing him. Even or do other pleasurable things such as watch television. She espe- when his mother removed all bleach from the house, the child no cially refused to eat foods that she considered ‘‘treats,'' such as longer allowed her to prepare his food, as he believed she was cookies and other foods with sugar. She insisted that her mother not ‘‘contaminated.'' When his father performed yard work using fer- pack treats in her lunch, and if her mother packed a treat anyway, tilizer, the child believed that his father was also now ‘‘contami- the child refused to eat it and would bring it home or give it away to nated.'' The child began to spit out or throw away any food that friends. During the structured interview, she admitted that she was touched his hands or lips. He constantly sought reassurance from somewhat preoccupied with her appearance and thought that an his parents by asking, ‘‘Is this bleach? Will bleach kill me?'' In unrealistically thin doll represented an ideal to which to aspire.
addition, he engaged in excessive showering, hand washing, and This patient was prescribed a 2 week course of amoxicillin by an tooth brushing behaviors. He would only eat food that was cut into outside physician * 3 weeks after symptom onset. Two weeks later long ‘‘french fry'' shapes so that he could pass the food into his (and 4 weeks prior to study enrollment), amoxicillin-clavulanic mouth without it touching his lips, and eventually he refused to eat acid was started by an outside physician for GAS prophylaxis; this completely. This contamination fear generalized to the point that he medication was continued throughout the duration of NIH study would not swallow even his own saliva, and would instead hold his participation as well. At NIH, this patient was treated with IVIG per saliva in his mouth at school until he could go to the bathroom and protocol at baseline and 6 weeks, and made a full recovery with spit it out. Because of intense contamination fears, the child had only slight residual generalized anxiety. Her parents reported that restricted his caloric intake to between 800 and 1000 calories daily, she was still a selective eater, but that her food intake was adequate.
without expressed desire to lose weight or dissatisfaction with hisbody. He also reported feeling hungry and was distressed by his Patient 24 was a 7-year-old girl with unremark- inability to eat, even expressing suicidal ideation when frustrated.
able premorbid medical or psychiatric history who presented to Upon entering the NIH study, this child was prescribed penicillin NIH with complaints of acute-onset OCD that began 9 months prior as prophylaxis against future GAS infections, and 2 g/kg of IVIG to evaluation. At that time, she abruptly displayed a compulsive over a course of 2 days. Six weeks later, the patient and his parents need to carry a plastic bucket at all times secondary to fears of reported a 90–95% improvement in his symptoms.
vomiting. She expressed fears of choking, and subsequently refusedto eat for 3 consecutive days. She developed fear of contaminants Patient 13 was an 8-year-old female who had a and fear that harm might come to her. She also became unchar- sudden onset of OCD symptoms including excessive confessing, acteristically irritable and aggressive, and she displayed severe concern with right and wrong, and contamination fears. She had separation anxiety, behavioral regression, inattentiveness, hyper- been exposed to GAS at school, and she and her fraternal triplet activity, and insomnia. A rapid GAS test performed at that time was sisters had flu-like symptoms, but she cultured negative for GAS negative, but she was prescribed cephalexin. The cephalexin had pharyngitis. At her baseline visit at NIH, her ASO was 403 (normal no discernible therapeutic effect; therefore, 5 days later the child's for age), and anti-DNAse B was elevated at 397. Historically the pediatrician discontinued cephalexin and prescribed a course of ‘‘healthiest'' of her siblings, the patient experienced a drastic amoxicillin. Within 36 hours of starting amoxicillin, the child was change in personality, with extreme perfectionism and concern described as ‘‘90% back to normal'' according to her parents.
with morals. She constantly confessed to doing something ‘‘wrong'' Amoxicillin was continued for 6 weeks, then stopped for 5 days, but or ‘‘bad'' on purpose, when in fact she had done nothing. She was resumed because of worsening behavior and anxiety, and then DISORDERED EATING IN PANDAS/PANS Table 2. Food-Related Symptoms and Behaviors DWeight in kilograms Food-related fears Food-related behaviors (% body weight change) Contamination fears: Germs; Restrictive eating Refusal of solid food; refusal to swallowsaliva Contamination fears: Germs; Refusal to eat unless father is present Fear of choking or vomiting Restrictive eating Contamination fears: Poison Restrictive eating Disgusted by smell and taste of Restrictive eating Contamination fears: Illicit Restrictive eating Contamination fears: Allergens Restrictive eating Contamination fears: Germs Refusal to consume food that has been in hishome Contamination fears: Germs Refused to eat or drink for 3 days; refusal to eat ordrink unless preparingit herself Contamination fears: Restrictive eating; refusal ‘‘Essence'' of others in food to swallow saliva Contamination fears: Bleach Would not allow food to Yes (value unavailable) touch his lips; eventualrefusal of solid food;refusal to swallowsaliva Feeling she didn't deserve to Restrictive eating Yes (value unavailable) eat or do pleasurable things,body image concerns Contamination fears: Poison Restrictive eating; refusal Yes (value unavailable) to swallow saliva Contamination fears: Germs Restrictive eating Contamination fears: Poison Refusal to eat for days Contamination fears: Germs Restrictive eating One episode of fear of choking Decrease in appetite Contamination fears: Germs Restrictive eating and Contamination fears: Germs; Restrictive eating Restrictive eating Yes (value unavailable) Would not disclose; concerns Restrictive eating Yes (value unavailable) about being overweight Contamination fears: Germs; Restrictive eating Contamination fears: Germs; Refusal to eat for 3 days fear of vomiting; fear ofchoking Refusal to eat for days Restrictive eating Fear of choking; Concerns of Refusal to eat; refusal to Contamination: Germs Restrictive eating; Contamination: Germs; Restrictive eating Concerns of beingoverweight aIndicates child was hospitalized secondary to dehydration.
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Table 3. Acute-Onset Neuropsychiatric Symptoms Inattention and/or hyperactivity Separation anxiety Behavioral regression Oppositional or aggressive behaviors Sensory sensitivity M, male; F, female; NIMH, National Institute of Mental Health; USF, University of South Florida.
continued for the next 5 months. Following exposure to a relative body weight, motivated behavior, and mood (Fetissov et al. 2005).
with a documented GAS infection, her symptoms suddenly re- Furthermore, animal models of antibodies to a-melanocyte stimu- turned and again included restricted eating secondary to contami- lating hormones have been found to correlate with feeding behavior nation fears and obsessions about choking. Rapid GAS testing was (Coquerel et al. 2012). OCD and anorexia are highly comorbid negative, and a culture was not obtained. Amoxicillin was contin- disorders, and structural and metabolic changes in the putamen and ued during this time, and a brief course of azithromycin was added caudate have been found in both groups (Rubenstein et al. 1992; by the child's pediatrician. Amoxicillin was continued during NIH Harrison et al. 2009; Radua et al. 2010; Kaye et al. 2011; Rothe- study enrollment, and in conjunction with a blinded infusion of mund et al. 2011; Friederich et al. 2012). In addition, antiputamen sham IVIG/placebo, produced a similar reduction in symptom se- antibodies have been discovered in children with OCD behaviors verity over the course of 8 weeks.
(Kirvan et al. 2006) and in adolescents with anorexia; serum pos-itivity was found in 6 out of 22 subjects with AN, five of whom hadcomorbid OCD (Harel et al. 2001), suggesting there may be a role of autoantibodies and immune factors in AN.
The children in this case series displayed acute-onset food re- Avoidant and restrictive food intake disorder (ARFID) is a new striction, and concomitant obsessions about contamination, poi- diagnosis in Diagnostic and Statistical Manual of Mental Dis- soning, vomiting, or choking. In some instances, disordered eating orders, 5th ed. (DSM-V) (American Psychiatric Association 2013).
appeared secondary to sensory issues or body image distortions. In Like other DSM-V disorders, the diagnostic criteria for ARFID addition to restricted food intake, the children also reported com- describe a specific clinical presentation, without regard for eti- pulsive ways of preparing food (e.g., cutting, smelling, arranging, ology, response to treatment, comorbid symptoms, or even acuity and ‘‘decontaminating'' food), restricting (e.g., avoiding foods of onset. The PANS cases described in this series met ARFID bases on texture, color, smell), or refusing food. Two thirds of the criteria, as there was a clear eating or feeding disturbance that led to children had obsessive fears about contaminated food or beverages, inadequate food intake, accompanied by weight loss in some pa- and five refused to swallow their saliva because of contamination tients, and significant psychosocial dysfunction in all patients.
Nearly all of the children in our series had a paralyzing fear of some Eighteen of the 29 cases (62%) had documented GAS infections adverse consequence of eating normally, as many felt food was at or shortly prior to the onset of behavioral symptoms; the re- poisoned or contaminated, or they had a fear they would vomit or maining 11 children had evidence of GAS exposure (n = 6) or had choke. Only three children expressed concerns about body image or another infection (n = 5). Evidence of recent exposure to MP was ‘‘getting fat,'' but these obsessions developed later in the course of demonstrated in one patient with a positive MP IgM (MP has been their symptoms. Because the children were so young, weight loss implicated in the development of neurologic sequelae [Yis that would be trivial in an adult (e.g., 1–3 kg) may have been 2008]). Notably, MP has been considered in the pathogenesis of tic physiologically significant, and the children were at higher risk of disorders (Mu¨ller et al. 2000, 2004) and is a proposed trigger for dehydration and electrolyte disturbances. One child was hospital- PANS (Swedo et al. 2012). Secondary symptoms such as enuresis, ized secondary to dramatic weight loss, and another required in- sleep disturbance, anxiety, and mood lability, as well as adventi- tious movements, are commonly associated with the onset of PANS As is shown in Table 4, ARFID would seem to capture the (Bernstein et al. 2010) and were frequently present in these cases eating disturbances described previously more accurately than (see Table 3).
AN or another specified feeding or eating disorder. ARFID can Molecular mimicry is one theory proposed in the etiology of be diagnosed with other psychiatric diagnoses such as OCD or PANDAS (Kirvan et al. 2006) and also has been postulated as a pseudodysphagia if the food restriction or avoidance is severe mediating factor in the development of restrictive eating disorders enough to be of clinical focus, or is an extreme characteristic of (Fetissov et al. 2005), as it is hypothesized that antibodies will cross the comorbid disorder. In addition, psychiatric conditions, in- the blood–brain barrier and provoke new onset psychiatric and cluding food restriction secondary to reactive attachment disor- neurological symptoms. Research has suggested that eating disor- der, autism spectrum disorder, trauma associated with choking, ders may be associated with autoantibodies against a-melanocyte and specific phobia must be considered, as symptoms of ARFID stimulating hormone, which is involved in appetite regulation, can be attributed to these primary diagnoses alone (Kreipe and DISORDERED EATING IN PANDAS/PANS Table 4. Comparison of AN, PANDAS ‘‘Anorexia,'' ARFID, and PANS Disordered Eating PANDAS ‘‘anorexia'' PANS disordered eating Insidious and usually Acute and prepubertalc,d,e Acute and prepubertal Acute and prepubertal (most common)f.g.h Females > > Malesi Females > Malesc,d,j Females < Males Genetic predisposition, Infection, genetic temperamental, genetic imbalance, cultural and physiologicalf,g,h Fears of being ‘‘fat,'' fear Contamination, sensory, Sensory, lack of interest in Contamination, sensory, of weight gain; body irrational thinking (e.g., food; conditioned irrational thinking image distortionsa food seems inedible, negative response to (e.g., food seems inedible, mechanical Slow, relapse common, Relatively rapid with Slow, need to address co- Relatively rapid with high mortality ratem morbidities f,g,h weight restoration aKaye 2008; bKlein and Walsh 2003; cSokol 2000; dSokol and Gray 1997; eCalkin and Carandang 2007; fFisher et al. 2014; gKreipe and Palomaki 2012; hNorris et al. 2014; iAmerican Psychiatric Association 2000; jSokol et al. 2002; kAmerican Psychiatric Association 2013; lStrober 1995; mHalmi et al. 2005.
AN, anorexia nervosa; PANDAS, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections; ARFID, avoidant/ restrictive food intake disorder; PANS, pediatric acute-onset neuropsychiatric syndrome.
Palomaki 2012). In addition, food neophobia, the avoidance of Clinical Significance trying new foods, was not found with our cases, as prior to the The cases described in this series demonstrate clinically im- onset of illness our patients consumed typical diets with a variety portant differences between the disordered eating of PANS and that of foods (Dovey et al. 2008). As with all psychiatric diagnoses, a of ARFID or AN. Acuity of onset, male prevalence, and young age medical condition must be ruled out as the primary cause of at presentation are the most striking differences, and serve to dis- the symptoms. Comorbid medical conditions with ARFID and tinguish the PANS patients from others with eating disorders. In the eating disorder-like presentations would include gastroparesis, PANS group, environmental factors, particularly GAS infections, low oral muscle tone or coordination, dysphagia, achalasia, can lead to a cascade of immunological, psychological, and phys- esophagitis, and irritable bowel syndrome. Other potential cau- ical symptoms that result in abrupt restriction and/or aversion to ses of presenting symptoms include food allergies and occult food. Early appropriate diagnosis and treatment of PANS is es- sential, as prompt treatment with antibiotics or immunomodulatorytherapies can produce dramatic symptom improvements. Further research is required to determine the best treatment practices fordisordered eating in the PANDAS/PANS cohort.
Eating disorders in children are on the rise, and the burden of these disorders on the healthcare system is high. Between 1999 and 2006, there was an 119% increase in eating disorder-relatedhospitalizations for children < 12 years of age, per an analysis Megan D. Toufexis, Rebecca Hommer, Diana M. Gerardi, Paul performed by the Agency for Healthcare Research and Quality Grant, Leah Rothschild, Precilla d'Souza, Kyle Williams, and (Rosen 2010). In particular, the steep rise in males with eating Susan E. Swedo have no financial relationships to disclose. James disorders is of concern (Carlat et al. 1997; Rosen 2003; Domine´ Leckman has received support from the NIH (salary and research et al. 2009). We hypothesize that the rise in eating disorders in funding), Tourette Syndrome Association (research funding), Gri- young children, especially in males, as suggested by our cases, fols, LLC (research funding), and Klingenstein Third Generation may be linked to a PANS presentation that could be missed by Foundation (medical student fellowship program). He receives clinicians. It is noteworthy that there exists a preponderance of book royalties from John Wiley and Sons, McGraw Hill, and Ox- males with pediatric OCD (Geller and March 2012) as well as ford University Press. Tanya Murphy has received research support PANS (Swedo et al. 2012); the male preponderance seen in our from All Children's Hospital Research Foundation, AstraZeneca sample may simply reflect what has been described for pediatric Neuroscience iMED, Centers for Disease Control, International OCD. It is our hope that a PANS diagnosis will be considered in OCD Foundation (IOCDF), NIH, Ortho McNeil Scientific Affairs, children who develop acute-onset food avoidance or restriction.
Otsuka, Pfizer Pharmaceuticals, Roche Pharmaceuticals, Shire, The management and outcome of children with a PANS pre- Sunovion Pharmaceuticals Inc., Tourette Syndrome Association, sentation differ from those for AN and ARFID, as treatment and Transcept Pharmaceuticals, Inc. Dr. Murphy is on the Medical with antibiotics or immunomodulatory therapies is often cura- Advisory Board for Tourette Syndrome Association and on tive (Perlmutter et al. 1999; Murphy and Pichichero 2002; the Scientific Advisory Board for IOCDF and for the PANDAS Snider et al. 2005; Murphy et al. in press), as in the cases de- Network. She receives a textbook honorarium from Lawrence scribed above.
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