Case example Tyler, an 11-year-old boy, was evaluated for a 2-year history of daily abdominal pain, with associated complaints of nausea, bloat- ing, and early satiety. His clinical history was p ositive for asthma, seasonal allergies, attention defi cit hyperactivity disorder, and sign ifi cant problems with sleep duration and quality. Tyler was being home-schooled and missed extracurricular/social activities several times per week due to pain. Past medical history included evaluation by a gastroenterologist and a naturopathic practitioner, with extensiv e laboratory testing plus upper and lower endoscopy. Review of Tyler \200\231s previous wor kup revealed normal lab fi ndings, but increased duodenal eosinophil counts on endoscopic b iop- sies. He had been tried on multiple medications and followed a restricted diet without signifi cant symptom relief. Intensive outpatient/inpatient rehabilitation In the event that coordinated outpatient trea tment as already described is not suffi cient \200\224that is, a child continues to experi- ence signifi cant pain symptoms and, more importantly, continues to suff er precipitous de clines in his or her functioning \200\224a higher level of treatment may be needed. Intensi ve day treatment or inpatient pain rehabilitation programs may represent a useful model of care in these cases. Such programs typically utilize all of the modalities previously descr ibed, albeit in a more struc- tured, controlled environment to help patients and their pare nts to \200\230walk the walk \200\231 in real time and in the context of a supportive, the rapeutic environment. Th e ultimate goal for these patients is to return to their homes, sc hools, and friends and transition back to their outpatient care team for monitoring and bui lding upon gains made. Tyler \200\231s evaluation and initial treatment took place over a period of approximately 4 months. A few of the components considered pivotal in Tyler \200\231s treatment are highl ighted here. Tyler was diag- nosed with FD using the Rome III criteria. In addition to anti - histamines and montelukast, he was prescribed oral cromolyn four times daily to address t he identifi ed infl ammatory compo- nent of his abdominal pain. Tyler also was referred to a certifi ed biofeedback practitioner near his home. He attended BART ses- sions three time s per week initially and practiced the skills several times per day at home. Tyler \200\231 s family utilized a structured plan for graduated school re-entry, starting by attending on e consist- ent class period daily and gradually adding time to his in-school schedule as st amina increased. During this process, Tyler also received instruction from a homebound teac her in the classes he was not yet attending. As specifi c classes were added to his in-scho ol schedule, support for these classes was dropped from homebound and the amount of homebou nd instruction was reduced. Accommodations also were put in place that allowed Tyler to tak e breaks for BART practice and to use the toilet, as needed, during the school day. Unfortunately, only a few, uncontrolled studies have examined the eff ectiveness of such pr ograms. Results from three prospec- tive studies of two diff erent 3-week multidisciplinary inpatient pro- grammes for pediatric chronic pain suggested improvements in pain intensity , pain-related disability, and school attendance, as well as in patients \200\231 emotional distress and pain-related coping (Eccleston et al., 2003 ; Hechler et al., 2009 , 2010 ). A recent retrospective review of an inpatient pediatric pain treatment program also documen ted improvements in school status, sleep, functional dis- ability, physical mobility, and m edication usage aft er a mean stay of 27 days (Maynard et al., 2010 ). While these results are encouraging CHAPTER 29 recurrent abdominal pain 295 Claar , R. L. , Walker , L. S. , and Smith , C. A. ( 1999 ). Functional disability in adole scents and young adults with symptoms of irritable bowel syndrome: the role of academic, so cial, and athletic competence . J Pediatr Psychol , 24 , 271 \200\223280. Routine in-offi ce follow-up continued on a regular basis to monitor progress, provide beha vioral coaching, support contin- ued engagement in treatment components, and modify the pla n as needed. Aft er 1 month of treatment, Tyler reported that BART was extremely helpful to him in terms of helping to manage his pain. Aft er 4 months of treatment, Tyler reported h aving abdom- inal pain about once per week. His appetite, sleep, energy, and headaches also were improved. Within approximately 8 weeks of beginning graduated school re-entry, Tyler was attending school full time and participating in social activities with his peers. Crushell , E. , Rowland , M. , Doherty , M. , Gormally , S. , Harty , S. , and Bourke , B. E. ( 2003 ). Importance of parental conceptual model of illness in severe recurrent abdomin al pain . Pediatrics , 1368 \200\2231372. Devanarayana , N. M. , De Silva , D. G. H. , and De Silva , H. J. ( 2008 ). Gastric myoelec trical and motor abnormalities in children and adolescents with functional recurrent abdomi nal pain . J Gastroenterol Hepatol , 23 , 1672 \200\2231677. Devanarayana , N. M. , Mettananda , S. , Liyanarachchi , C. , Nanayakkara , N. , Perera , N . , and Rajindrajith , S. ( 2011 ). Abdominal pain-predominant functional gastrointestinal diseases in children and adolescents: prevalence, symptomatology, and association with emot ional stress . J Pediatr Gastroenterol Nutr , 53 , 659 \200\223665. It is important to convey the fact that Tyler \200\231s recovery was not perfectly linear, nor has it ended. Although not yet substanti- ated in the literature, clinical experience h as suggested that eosinophilic infl ammation within the gastrointestinal tract is especiall y sensitive to viral illnesses, seasonal allergies, and stress. Consistent with this, Tyler evidenced temporary symptom fl ares at predictable times during his treatment. While certa inly disap- pointing for Tyler and his family, these setbacks provide impor- tant clues for preventing, or at least managing, fl ares when they occur. Proper hand washing to reduce t ransmission of viruses, aggressive treatment of seasonal allergies, and advance plan- ning to reduce stress can be helpful in reducing the odds of a temporary increase in gastrointes tinal infl ammation and associ- ated symptoms. Identifying and addressing potential trigger s for future episodes can be an important part of long-term mainte- nance for an individual child. Devanarayana , N. M. , Rajindrajith , S. , Rathnamalala , N. , Samaraweera , S. , and Benni nga , M. A. ( 2012 ). Delayed gastric emptying rates and impaired antral motility in childr en fulfi lling Rome III criteria for functional abdominal pain . Neurogastroenterol Motil , 24 (5), 420 \200\223425. Di Lorenzo , C. , Colletti , R. B. , Lehmann , H. P. , Boyle , J. T. , Gerson , W. T. , Hya ms , J. S. , et al . ( 2005 a). Chronic abdominal pain in children: a clinical report of th e American Academy of Pediatrics and the North American Society for Pediatric Gastroenterol ogy, Hepatology, and Nutrition . J Pediatr Gastroenterol Nutr , 40 , 245 \200\223248. Di Lorenzo , C. , Colletti , R. B. , Lehmann , H. P. , Boyle , J. T. , Gerson , W. T. , Hya ms , J. S. , et al . ( 2005 b). 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Parental response to child illness behavior . J Pediatr Psychol , 17 , 49 \200\22371. Ruepert , L. , Quartero , A. O. , de Wit , N. J. , van der Heijden , G. J. , Rubin , G. , a nd Muris , J. W. ( 2011 ). Bulking agents, antispasmodics, and antidepressants for the trea tment of irritable bowel syndrome . Cochrane Database Syst Rev , 8 , CD003460 . Walker , L. S. , Lipani , T. A. , Greene , J. W. , Caines , K. , Stutts , J. , Polk , D. B. , et al . ( 2004 ). Recurrent abdominal pain: Symptom subtypes based on the Rome II criter ia for pediatric functional gastrointestinal disorders . J Pediatr Gastroenterol Nutr , 38 , 187 \200\223191. CHAPTER 29 recurrent abdominal pain 297 Youssef , N. N. , Atienza , K. , Langseder , A. L. , and Strauss , R. S. ( 2008 ). Chronic abdominal pain and depressive symptoms: analysis of the national longitudinal study of adol escent health . Clin Gastroenterol Hepatol , 6 , 329 \200\223332. Walker , L. S. , Williams , S. E. , Smith , C. 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Prevalence and associ ated factors of functional gastrointestinal disorders and bowel habits in Chinese adolescen ts; a school-based study . J Pediatr Gastroneterol Nutr , 53 , 168 \200\223173. Wood , J. D. ( 2004 ). Enteric neuroimmunophysiology and pathophysiology . Gastroenterology , 127 , 635 \200\223637. CHAPTER 30 Chronic pelvic pain in children and adolescents Susan L. Sager and Marc R. Laufe r Summary Pain due to pelvic pathology in children and adolescents is oft en described as abd ominal pain, and frequently coexists with gastroin- testinal symptoms due to neuronal cross talk and viscero-viscero or viscero-somatic convergence of sensory aff erents. Dysmenorrhe a is highly prevalent among adolescents yet is underreported. Like many chronic conditions where repetitive noxious stimuli are present, dysmenorrhea can be associated with central s ensitization of pain pathways and visceral hyperalgesia. In this chapter the com- ponents o f a menstrual history, the importance of obtaining a men- strual history in adolescents wit h abdominopelvic pain, and the indications for referral to an adolescent gynecologist are d iscussed. Endometriosis should be considered in the diff erential diagnosis of all females with chronic abdominopelvic pain of undetermined etiology once the benchmark of thelarche h as been met. Other overlooked causes of abdominopelvic pain include intercostal or subcosta l neuralgias, nerve compression, and abdominal cutane- ous nerve entrapment. A multidiscipl inary approach to treatment of the patient with chronic abdominopelvic pain is discussed. syndrome (IBS) or functional gastrointestinal disorder (FGID) prior to identifying other pe lvic pathology. Chronic pelvic pain is associated with changes in the neuronal processing of pain signals i n the periphery, dorsal horn, and brain. Pain oft en persists long aft er the initiating pe lvic infl ammation or trauma is resolved. Patients referred for treatment of chronic pel- v ic pain may have histories that include visceral or musculoskel- etal pathology but those i nitial inciting events have resolved or are being treated eff ectively by all measures. Fur ther evaluations are oft en non-revealing of active pathology, and a functional disorder su ch as IBS becomes the referring diagnosis to the pain specialist. Central sensitization wit h development of visceral hyperalgesia can provide a framework for understanding why IBS is diagnosed so frequently in patients with pelvic pathology and why patients with pelvic pat hology report gastrointestinal symptoms so frequently. Causes of chronic pelvic pain Th e diff erential diagnosis of abdominopelvic pain is extens ive and includes orthopedic, gastrointestinal, gynecological, urological, traumatic, infect ious, and neoplastic causes. A careful history will help direct the evaluation. Irritable b owel syndrome and stress are the most common diagnoses received by women with chronic pel- vic pain, though many are diagnosed without any investigative tests (Zondervan et al., 2001 ). Th e most common causes of chronic pel- vic pain in adolescent females are dysmenorrhea and constipation. Introduction Pelvic and abdominal pain is a common complaint in paediat- ric and adolescent primary care, and in some cases, persists into adulthood (Campo et al., 2001 ; Walker et a l., 1995 ). Pelvic pain is a broad term that encompasses pain originating from viscera with in the pelvic cavity, and from the myofascial and bony structures that comprise the pelvis. Pain due to pelvic pathology can be referred to other viscera, the back, abdominal wall, a bdomen, hips, and upper thighs, refl ecting a broad viscero-viscero and viscero-somatic dis - tribution of the sensory and sympathetic aff erent neurons of the lumbosacral plexus ( Fi gure 30.1 ). For many young patients, the dis- tinction between pelvic and abdominal pain i s not well appreciated and descriptions of abdominopelvic pain can be highly variable. Acco rdingly, it is not uncommon for adolescents to describe pain due to pelvic pathology as \200\230stomach ache, \200\231 and also report symptoms of nausea, gastro-oesophageal refl ux, constipation, and bloating in addition to abdominopelvic pain. Not surprisingly, many y oung adolescents with these non-specifi c symptoms are evaluated fi rst by gastroenterologi sts and oft en have a diagnosis of irritable bowel Dysmenorrhea Dysmenorrhea is a syndrome characterized by recurrent, crampy, lower abdominal pain occurring during menses. Pain is oft en accompanied by nausea, vomiting, diarrhea, he adaches, and muscular cramps, and frequently co-occurs with other chronic pain conditions, including migraine, IBS, interstitial cystitis, fi bromyalgia, and chronic fatigue syndrome (Alagiri et al., 1997 ). Dysmenorrhea aff ects up to 90% of post-menarchal adolescents, wi th 9% to 14% reporting pain as severe (Klein and Litt, 1981 ), and is the leading reason fo r missed school days and work in the ado- lescent population (Schroeder and Sanfi lippo, 19 99 ). Yet, under- reporting of symptoms is common and many adolescents do not seek treatmen t for dysmenorrhea even when symptoms are severe and school days are missed (Klein and Litt , 1981 ). It is speculated CHAPTER 30 chronic pelvic pain in children and adolescents 299 Central nervous system changes associated with dysmenorrhea lead to sensitization of other abdominopelvic viscera and somatic tissues, including bladder, intestine, abdominal wall, a nd back (Giamberardino et al., 1997 ). Animal studies have demonstrated that acute infl amm ation in one pelvic organ (uterus, colon or blad- der) will induce infl ammatory changes in either nearby or remote organs and aff ect the function of those organs (Berkley, 2005 ). Th is observation has been referred to as a \200\230cross-organ aff ect \200\231 and sup- ports data from other studies demonstrating viscero-visceral con- vergence of sensory and s ympathetic neurons in the spinal cord (Winnard et al., 2006 ). Maxillary nerce Clliary ganglion Sphenopalatine ganglion Superior cervical ganglion of sympathetic Cervical plexus Pharyngeal plexus Middle cervical ganglion of sympathetic Inferior cervical ganglion of sympathetic Recurrent nerve Brachial plexus Based on a history of pain with menses, the diff erential is limited. Th e majority of case s of dysmenorrhea in adolescents are primary, with normal ovulatory cycles and no associate d pelvic pathology. Secondary dysmenorrhea refers to painful menstruation associ- ated with pelvic abnormalities, which may be seen in about 10% of adolescents with dysmenorrhea. Ref erral to a gynecologist is indicated for evaluation and treatment of severe dysmenorrhea an d to rule out the possibility of an obstructive or partially obstruc- tive anomaly such as a transverse vaginal septum, microperforate hymen, or obstructed hemivagina or hemiuterus. When a gynaeco- logical exam is indicated, unlike in adults, the exam is oft en limited to a cotton swab inserted into the hymenal orifi ce to help deter- mine if there is an anomaly of the vagina. If there is still concern a transabdominal ultrasound can be helpful. Bronchial plexus Cardiac plexus Esophageal plexus Coronary plexuses Left vagus nerve Greater splanchnic nerve Gastric plexus Caliac plexus Lesser splanchnic nerve Superior mesentric plexus Dysmenorrhea is typically initially treated with non-steroidal anti-infl ammatory drugs (NS AIDs; Marjoribanks et al., 2010 ). If pain persists then hormonal therapy is used to lighte n periods and decrease pain. Th is is achieved with either combination estrogen/ progestin hormonal pills or progestin-only therapy. Progestin-only therapy is typically utilized if t here is a contraindication to the use of estrogen such as in the case of migraine headaches with focal neurological symptoms or a history of a thrombophilia. If pain resolves with th e use of NSAIDs and cyclic hormonal therapy then no further evaluation is usually needed. I f pain persists on NSAIDs and hormonal therapy then laparoscopic evaluation is warranted to evaluate for the possibility of endometriosis as the underlying diag- nosis. Approximately 70% of adolescents who have a persistence of pain on NSAIDs and 3 months of cyclic hormona l therapy who undergo a laparoscopy have endometriosis (Laufer et al., 1997 ). Aortic plexus Inferior mesenteric plexus Lumbar plexus Hypogastric plexus Sacral plexus Pelvic plexus Bladder Vesical plexus Figure 30.1 Anatomy of the nerve supply to the abdomen and pelvis. Reproduced from Henry Gr ay, Anatomy of the Human Body , 1918 edition, Copyright 1918, with permission from Elsev ier. that many adolescents consider dysmenorrhea a variant of normal, which in part explains und erreporting and why epidemiological data on treatment outcomes in young adolescents is lack ing. In addition, many adolescents are hesitant to discuss gynecological issues and have co ncerns that if they do verbalize their symptoms they may need a bimanual or speculum-assist ed pelvic exam. Endometriosis Endometriosis is a chronic infl ammatory and painful condition defi ned as th e presence of uterine glands and stroma outside the uterus. Th ere is no clear understandin g as to how endometrio- sis causes pain but proposed explanations include prostaglan- din p roduction, cytokine production, and adhesion formation. Endometriosis lesions can be found anywhere within the abdomi- nal and pelvic cavity. Most lesions are seen on the ovaries, pe lvic walls and cul-de-sac, but can also be found on bowel, bladder, ureters, liver, lung, a nd scar tissue. Th ere are no laboratory tests or imaging studies diagnostic for endometrio sis, and thus adolescent endometriosis is diagnosed by laparoscopic visualization. Dysmenorrhea is a cyclic pain, and recurrent nociceptive input from painful periods each mo nth can lead to neuronal alterations at the level of the spinal cord and brain that persist throughout the menstrual cycle (Vincent et al., 2011 ). Studies in adults with dysmenorrhe a have demonstrated central nervous system changes similar to those seen in other chronic p ain conditions. Such changes include altered central processing of noxious stimuli (Vincent et al., 2011 ), metabolic and morphological changes in the brain as seen on imaging studie s (Tu et al., 2009 , 2010 ), alterations in hypoth- alamic \200\223pituitary \200\223adreno cortical axis function, and reduced qual- ity of life (Vincent et al., 2011 ). Dysmenorrhea is therefore a cyclic pain that appears to develop features of a chronic neuropathic pain condition over time. In adult women, the most common cause of chronic pelvic pain is endometriosis (Fauconnier a nd Chapron, 2005 ), estimated to aff ect 4% to 17% of post-menarchal females (Ranney, 1980 ). Population studies of endometriosis in adolescents are likely to underestimate its preva lence due to underreporting of symptoms and failure to diagnose. In adolescents who seek tr eatment for unexplained SECTION 4 pain in specific populations and diseases 300 chronic pelvic pain, there is a 47% prevalence rate of endometriosis found at time of lapar oscopy (Goldstein et al., 1979 ). Other studies have shown that 25% to 38% of adolescents w ith chronic pelvic pain who seek medical care and undergo laparoscopy have endometrio- sis (Kontoravdis et al., 1999 ; Vercellini et al., 1989 ). Empiric treat- ment with NSAIDs and oral contraceptives (for the treatment of dysmenorrhea as described earlier) can improve sy mptoms for many adolescents with chronic pelvic pain, but in cases where pain persists, gre ater than 70% of adolescents with chronic pelvic pain will be diagnosed with endometriosis (Laufer et al., 2003 ). In a more recent study, 97% of adolescents with persistence of pain on NSAIDs and combination hormonal therapy were found to have endometriosis on laparoscopi c evaluation (Opoku-Anane and Laufer, 2012 ). Th e increase in prevalence from 70% to 97% m ay be due to the improvement of optics of laparoscopes with digital imaging. ovarian cysts more frequently than controls without endometriosis (Ballard et al., 2008 ). Women experiencing these symptoms have a high risk of having endometriosis, especially if t hey experience more than one of these symptoms (Ballard et al., 2008 ). While ado- lescents may report similar symptoms as adults, 60% of adolescents with endometriosis report either abdominal or pelvic pain, and 90% report pain that occurs during menses (cyclic) as well a s pain that is continuous throughout the menstrual cycle (acyclic) (Laufer et al., 1997 ). Questioning adolescents about their menstrual history can iden- tify markers associated wit h endometriosis (Chapron et al., 2011 ). A positive family history of endometriosis in a fi rst-degree rela- tive (odds ratio (OR) = 3.2; 95% confi dence interval (CI): 1.2 \200\2238 .8) school absenteeism during menstruation (OR = 1.7; 95% CI: 1 \200\2233), and use of oral contraceptive pills for treating severe primary dys- menorrhea in girls under18 years (OR = 4.2; 95% CI: 1.8 \200\22310.0) are predictive for endometriosis (Chapron et al., 2011 ). Although commonly understood to be a disease of adult women, endometriosis can occur in ado lescents and in pre-menarchal girls as early as 8 years of age (Marsh and Laufer, 2005 ). A s endome- triosis is an estrogen-dependent disease, endometriosis should be considered in t he diff erential diagnosis of all females with abdomi- nal or pelvic pain once the benchmar k of thelarche has been met (Economy and Laufer, 1999 ; Lubianca et al., 1998 ). More typic ally, women are diagnosed during their childbearing years when they seek medical treatment for infertility. However, data from the Endometriosis Association indicate that two-thirds of adult women with endometriosis reported onset of pelvic symptoms during ado- lescence, w ith 38% reporting symptom onset before age 15 years (Ballweg, 2004 ). On average there is a delay of 9 years from onset of symptoms to diagnosis of endometriosis, with longer delays (8 \200\22310 years) diagnosing adolescents compared to women in their 30s (<2 years; Ballw eg, 2004 , Hadfi eld et al., 1996 ). Adolescents under age 15 years with chronic pelvic pai n saw an average of 4.2 doctors compared with women in their early 30s who saw an aver- age of 2.6 doctors before diagnosis or referral (Ballweg, 2004 ). Many women with endometriosis report a preponderance of gas- trointestinal symptoms and hav e received a previous diagnosis of IBS or pelvic infl ammatory disease (PID) which contribu tes to the delay in diagnosis of endometriosis in both adults and adolescents. In a consecu tive series of 355 women undergoing laparoscopy for suspected endometriosis, 90% of the wom en with histologically confi rmed endometriosis had gastrointestinal symptoms (bloat- ing c onstipation, diarrhea, nausea, vomiting). While bloating was the most frequent gastrointest inal symptom, reported by 83% of women, 71% also had other gastrointestinal symptoms (Marou n et al., 2009 ). Gastrointestinal symptoms are reported nearly as fre- quently as gynecolo gical symptoms in women with endometrio- sis (Maroun et al., 2009 ). Similarly, a national case \200\223control survey from the UK concluded that 45% of women with endometriosis had a record of abdominal pain and only 15% had a record of pelvic pain (Ballard et al., 2008 ) . Results from the same study also showed that women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS and six times more likely to receive a diagnosi s of PID than women without endometriosis (Seaman et al., 2008 ). Th ere is no data specifi c for adolescents. Th e associa- tion between endometriosis and PID or IBS was less strong aft er the diagnosis of endometriosis was made, and these authors suggest some misdiagnosi s among women with endometriosis, while pos- ing the possibility of comorbidity between end ometriosis and PID or IBS. Whether IBS coexists with endometriosis or is secondary to devel opment of visceral hyperalgesia due to this chronic infl amma- tory disease is not known. A ccordingly, endometriosis should be considered in the diff erential diagnosis of all female s with abdomi- nal or pelvic pain when a functional gastrointestinal disorder such as IBS i s considered once the benchmark of thelarche has been met (Economy and Laufer, 1999 ). Adolescent endometriosis can be a challenging diagnosis as signs and symptoms are oft en no n-specifi c for gynecological pathology and can diff er from those reported by adults ( Tab le 30.1 ). Adult women with endometriosis report gynecological symptoms of abdominopelvic p ain, severe dysmenorrhea, menorrhagia, irregu- lar menses, subfertility or infertility, and acute adnexal pain due to Table 30.1 Symptoms of adolescents with endometriosis Presenting symptoms Per cent Acyclic and cyclic pain 62.5 Acyclic pain 28.1