Infection, immune function, and functional gut disorders
2004; Elsevier BV; Volume: 2; Issue: 6 Linguagem: Inglês
10.1016/s1542-3565(04)00159-4
ISSN1542-7714
Autores Tópico(s)Respiratory and Cough-Related Research
ResumoThe term functional diseases covers a broad range of symptom clusters in which the mechanism is poorly understood. Although most clinicians believe that in the majority of cases the main abnormality lies in the brain, with hypersensitivity to stimuli coming from the gut, it is likely that in these heterogeneous groups of patients there is also a proportion in whom the main abnormality is in the gut, but currently beyond our abilities to detect. Those patients who develop symptoms after infection/inflammation on the background of a previously normal bowel habit are more likely to fall into this latter category and are the main focus of this article, although as will become clear, central effects remain significant. After first considering general principles of how infection and inflammation can result in disordered function, this review considers the specific diseases listed in Table 1 and includes organic postinflammatory disorders that seem to show important mechanisms that might well apply to functional disorders.Table 1Disorders of Gastrointestinal Motor and Sensory Function After Known and Unknown Inflammatory InsultsDisorder of functionInflammatory insultEsophageal dysmotilityInfection by T. cruziDelayed gastric emptyingRotavirus infection, Lyme disease,34Pande H Lacy B.E Crowell M.D Inflammatory causes of gastroparesis report of five cases.Dig Dis Sci. 2002; 47: 2664-2668Crossref PubMed Scopus (24) Google Scholar post vaccination,34Pande H Lacy B.E Crowell M.D Inflammatory causes of gastroparesis report of five cases.Dig Dis Sci. 2002; 47: 2664-2668Crossref PubMed Scopus (24) Google Scholar cytomegalovirus,29Nowak T.V Goddard M Batteiger B Cummings O.W Evolution of acute cytomegalovirus gastritis to chronic gastrointestinal dysmotility in a nonimmunocompromised adult.Gastroenterology. 1999; 116: 953-958Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar herpes zoster,30Kebede D Barthel J.S Singh A Transient gastroparesis associated with cutaneous herpes zoster.Dig Dis Sci. 1987; 32: 318-322Crossref PubMed Scopus (30) Google Scholar Epstein-Barr virus,31Bityutskiy L.P Soykan I McCallum R.W Viral gastroparesis a subgroup of idiopathic gastroparesis—clinical characteristics and long-term outcomes.Am J Gastroenterol. 1997; 92: 1501-1504PubMed Google Scholar, 32Vassallo M Camilleri M Caron B.L Low P.A Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis.Gastroenterology. 1991; 100: 252-258PubMed Google Scholar human immunodeficiency virus33Konturek J.W Fischer H van dV I Domschke W Disturbed gastric motor activity in patients with human immunodeficiency virus infection.Scand J Gastroenterol. 1997; 32: 221-225Crossref PubMed Scopus (29) Google ScholarFunctional dyspepsiaPresumed infective39Tack J Demedts I Dehondt G Caenepeel P Fischler B Zandecki M et al.Clinical and pathophysiological characteristics of acute-onset functional dyspepsia.Gastroenterology. 2002; 122: 1738-1747Abstract Full Text Full Text PDF PubMed Scopus (229) Google ScholarIBSPostinfective IBS44Spiller R.C Postinfectious irritable bowel syndrome.Gastroenterology. 2003; 124: 1662-1671Abstract Full Text Full Text PDF PubMed Scopus (362) Google ScholarIBS in quiescent IBD76Isgar B Harman M Kaye M.D Whorwell P.J Symptoms of irritable bowel syndrome in ulcerative colitis in remission.Gut. 1983; 24: 190-192Crossref PubMed Scopus (218) Google Scholar, 77Simren M Axelsson J Gillberg R Abrahamsson H Svedlund J Bjornsson E.S Quality of life in inflammatory bowel disease in remission the impact of IBS-like symptoms and associated psychological factors.Am J Gastroenterol. 2002; 97: 389-396PubMed Google ScholarMyenteric ganglionitis56Tornblom H Lindberg G Nyberg B Veress B Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome.Gastroenterology. 2002; 123: 1972-1979Abstract Full Text Full Text PDF PubMed Scopus (409) Google ScholarGuillain-Barré syndrome complicated by ileus pseudo-obstructionPostinfectious polyneuropathy,87Burns T.M Lawn N.D Low P.A Camilleri M Wijdicks E.F Adynamic ileus in severe Guillain-Barre syndrome.Muscle Nerve. 2001; 24: 963-965Crossref PubMed Scopus (48) Google Scholar herpes zoster57Pui J.C Furth E.E Minda J Montone K.T Demonstration of varicella-zoster virus infection in the muscularis propria and myenteric plexi of the colon in an HIV-positive patient with herpes zoster and small bowel pseudo-obstruction (Ogilvie's syndrome).Am J Gastroenterol. 2001; 96: 1627-1630Crossref PubMed Google ScholarNeuroimmune appendicitisResolved acute appendicitis89Di Sebastiano P Fink T Di Mola F.F Weihe E Innocenti P Friess H Buchler M.W Neuroimmune appendicitis.Lancet. 1999; 354: 461-466Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 90Bouchard S Russo P Radu A.P Adzick N.S Expression of neuropeptides in normal and abnormal appendices.J Pediatr Surg. 2001; 36: 1222-1226Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 91Nemeth L Reen D.J O'Briain D.S McDermott M Puri P Evidence of an inflammatory pathologic condition in "normal" appendices following emergency appendectomy.Arch Pathol Lab Med. 2001; 125: 759-764PubMed Google ScholarSymptomatic diverticular diseaseAcute diverticulitis95Simpson J Neal K.R Scholefield J.H Spiller R.C Patterns of pain in diverticular disease and the influence of acute diverticulitis.Eur J Gastroenterol Hepatol. 2003; 15: 1005-1010Crossref PubMed Scopus (93) Google Scholar Open table in a new tab The gut is a richly innervated organ and it is likely that most disorders of function involve disturbance of either efferent or afferent neural function. This can be either nonspecific neuronal damage caused by chronic inflammation or specific damage (e.g., caused by neurotrophic viruses) or to immune damage caused by cross-reacting antigens as seen in the Guillain-Barré syndrome after Campylobacter jejuni.1Mishu B Blaser M.J Role of infection due to Campylobacter jejuni in the initiation of Guillain-Barre syndrome.Clin Infect Dis. 1993; 17: 104-108Crossref PubMed Scopus (123) Google Scholar Tissue damage usually is followed by repair in which nerve regrowth plays a vital role. These regenerating nerves often exhibit an altered phenotype that may be associated with increased sensitivity. Other possible mechanisms of dysfunction are listed in Table 2, but evidence of these mechanisms, well described in animal models, is sparse in humans.Table 2Mechanisms and Mediators of Altered Gastrointestinal Function After InflammationMechanismsMediatorsClinical examplesNeuronal lossAcute inflammatory productsAcute diverticulitis,96Simpson J Haji-Suyoi A Jenkins D Scholefield J.H Spiller R.C Quantification of neurological changes in resection specimens with complicated and uncomplicated diverticular disease.Gastroenterology. 2002; 122 (abstr): M1506Google Scholar acute appendicitis89Di Sebastiano P Fink T Di Mola F.F Weihe E Innocenti P Friess H Buchler M.W Neuroimmune appendicitis.Lancet. 1999; 354: 461-466Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 90Bouchard S Russo P Radu A.P Adzick N.S Expression of neuropeptides in normal and abnormal appendices.J Pediatr Surg. 2001; 36: 1222-1226Abstract Full Text Full Text PDF PubMed Scopus (14) Google ScholarNeurotrophic virusHerpes zoster,30Kebede D Barthel J.S Singh A Transient gastroparesis associated with cutaneous herpes zoster.Dig Dis Sci. 1987; 32: 318-322Crossref PubMed Scopus (30) Google Scholar Epstein-Barr,31Bityutskiy L.P Soykan I McCallum R.W Viral gastroparesis a subgroup of idiopathic gastroparesis—clinical characteristics and long-term outcomes.Am J Gastroenterol. 1997; 92: 1501-1504PubMed Google Scholar, 32Vassallo M Camilleri M Caron B.L Low P.A Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis.Gastroenterology. 1991; 100: 252-258PubMed Google Scholar human immunodeficiency virus33Konturek J.W Fischer H van dV I Domschke W Disturbed gastric motor activity in patients with human immunodeficiency virus infection.Scand J Gastroenterol. 1997; 32: 221-225Crossref PubMed Scopus (29) Google ScholarAutoimmuneGuillain-Barré syndrome87Burns T.M Lawn N.D Low P.A Camilleri M Wijdicks E.F Adynamic ileus in severe Guillain-Barre syndrome.Muscle Nerve. 2001; 24: 963-965Crossref PubMed Scopus (48) Google ScholarAltered nerve phenotype (increased substance P, VR1 expression, galanin)Nerve growth factors (GDNGF)Crohn's disease/ulcerative colitis,81Watanabe T Kubota Y Muto T Substance P containing nerve fibers in rectal mucosa of ulcerative colitis.Dis Colon Rectum. 1997; 40: 718-725Crossref PubMed Scopus (41) Google Scholar, 82Kubota Y Petras R.E Ottaway C.A Tubbs R.R Farmer R.G Fiocchi C Colonic vasoactive intestinal peptide nerves in inflammatory bowel disease.Gastroenterology. 1992; 102: 1242-1251Abstract PubMed Google Scholar, 83Belai A Boulos P.B Robson T Burnstock G Neurochemical coding in the small intestine of patients with Crohn's disease.Gut. 1997; 40: 767-774Crossref PubMed Scopus (165) Google Scholar, 84Schneider J Jehle E.C Starlinger M.J Neunlist M Michel K Hoppe S Schemann M Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non-inflamed rectum of patients with Crohn's disease.Neurogastroenterol Motil. 2001; 13: 255-264Crossref PubMed Scopus (121) Google Scholar neuroimmune appendicitis89Di Sebastiano P Fink T Di Mola F.F Weihe E Innocenti P Friess H Buchler M.W Neuroimmune appendicitis.Lancet. 1999; 354: 461-466Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 90Bouchard S Russo P Radu A.P Adzick N.S Expression of neuropeptides in normal and abnormal appendices.J Pediatr Surg. 2001; 36: 1222-1226Abstract Full Text Full Text PDF PubMed Scopus (14) Google ScholarIncreased gut permeabilityCytokinesAltered muscle function (hypertrophy/responsiveness)T lymphocytes, increased macrophages, increased cyclooxygenase-2Diverticular disease97Simpson J Sundler F Jenkins D Spiller R.C Increased expression of galanin in mucosal nerves of patients with painful diverticular disease.Gut. 2003; 52: 318Crossref PubMed Scopus (11) Google Scholar PI-IBS49Spiller R.C Jenkins D Thornley J.P Hebden J.M Wright T Skinner M et al.Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.Gut. 2000; 47: 804-811Crossref PubMed Scopus (981) Google ScholarGDNGF, glial-derived nerve growth factor. Open table in a new tab GDNGF, glial-derived nerve growth factor. Rodent models of experimental inflammation have lead to an enormous explosion in knowledge about the effects of inflammation in the gut, mostly relevant to the acute effects but some also examining the long-term effects that will be of most relevance to this article. Animal models of gastrointestinal infection, which can be used to study long-term effects, are in short supply because many of the known pathogens (e.g., C. jejuni) fail to cause disease in experimental animals or cause unacceptable mortality. Therefore, most investigators have used either parasitic infections (Trichinella spiralis or Nippostrongylus brasiliensis) or chemical agents such as trinitrobenzene sulfonic acid or acetic acid. Damage to the barrier function of the gut or direct invasion of the tissue allows bacterial products such as lipopolysaccharide and chemotactic peptides to up-regulate key transcription factors such as nuclear factor κ B, inducing secretion of inflammatory cytokines including interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor, and adhesion molecules. This is followed by recruitment of circulating polymorphonuclear leukocytes, lymphocytes, and monocytes. When these activated cells enter the tissue, they release a range of inflammatory mediators, resulting in tissue destruction and release of adenosine triphosphate, H+, prostaglandins, K+, and bradykinins, which form part of the inflammatory soup. This destructive process, which damages nerves as well as other structures, is followed by remodeling, which ultimately is followed by down-regulation of inflammation and tissue healing. Similar processes have been documented after dental abscess formation,2Byers M.R Swift M.L Wheeler E.F Reactions of sensory nerves to dental restorative procedures.Proc Finn Dent Soc. 1992; 88: 73-82PubMed Google Scholar pulmonary infections,3Martinez F.D Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma.Pediatr Infect Dis J. 2003; 22: S76-S82PubMed Google Scholar and urinary tract infections,4Bauer S.B Special considerations of the overactive bladder in children.Urology. 2002; 60: 43-48Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar all of which may be followed by hypersensitivity and irritability. This increased sensitivity involves both increased firing by nociceptive sensory afferents as well as the recruitment of other previously silent nociceptors.5Mayer E.A Gebhart G.F Basic and clinical aspects of visceral hyperalgesia.Gastroenterology. 1994; 107: 271-293Abstract PubMed Google Scholar Mediators of these effects include adenosine diphosphate, bradykinin, prostaglandins, serotonin, nerve growth factor, and substance P, all of which are capable of sensitizing visceral nerves.6Bueno L Fioramonti J Visceral perception inflammatory and non-inflammatory mediators.Gut. 2002; 51: i19-i23Crossref PubMed Scopus (100) Google Scholar Inflammation is accompanied by local up-regulation of relevant receptors such as purinergic receptor type 2X3,7Bland-Ward P.A Humphrey P.P P2X receptors mediate ATP-induced primary nociceptive neurone activation.J Auton Nerv Syst. 2000; 81: 146-151Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar neurokininin 1 receptor,8Pothoulakis C Castagliuolo I Leeman S.E Wang C.C Li H Hoffman B.J Mezey E Substance P receptor expression in intestinal epithelium in clostridium difficile toxin A enteritis in rats.Am J Physiol. 1998; 275: G68-G75PubMed Google Scholar vanilloid receptor 1 (VR1),9Yiangou Y Facer P Dyer N.H Chan C.L Knowles C Williams N.S et al.Vanilloid receptor 1 immunoreactivity in inflamed human bowel.Lancet. 2001; 357: 1338-1339Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar nerve growth factor receptor tyrosine kinase A,10Di Mola F.F Friess H Zhu Z.W Koliopanos A Bley T Di Sebastiano P et al.Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease.Gut. 2000; 46: 670-679Crossref PubMed Scopus (123) Google Scholar and simultaneous facilitation in spinal pain pathways. A variety of antagonists have been shown to be effective in acutely reducing hypersensitivity, including antagonists of tachykinins, calcitonin gene-related peptide, nerve growth factor, protease activated receptor 2, and bradykinin, some of which currently are being evaluated in clinical trials in humans. The later phases of the inflammatory response are characterized by infiltration with macrophages and lymphocytes. These have been shown to have profound effects on neural function,11Barbara G De Giorgio R Deng Y Vallance B Blennerhassett P Collins S.M Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice.Gastroenterology. 2001; 120: 1729-1736Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 12Swain M.G Blennerhassett P.A Collins S.M Impaired sympathetic nerve function in the inflamed rat intestine.Gastroenterology. 1991; 100: 675-682Abstract PubMed Google Scholar, 13Vallance B.A Collins S.M The effect of nematode infection upon intestinal smooth muscle function.Parasite Immunol. 1998; 20: 249-253Crossref PubMed Scopus (23) Google Scholar including impaired release of norepinephrine from inhibitory sympathetic nerves12Swain M.G Blennerhassett P.A Collins S.M Impaired sympathetic nerve function in the inflamed rat intestine.Gastroenterology. 1991; 100: 675-682Abstract PubMed Google Scholar, 13Vallance B.A Collins S.M The effect of nematode infection upon intestinal smooth muscle function.Parasite Immunol. 1998; 20: 249-253Crossref PubMed Scopus (23) Google Scholar together with enhanced muscular activity in response to cholinergic stimuli.13Vallance B.A Collins S.M The effect of nematode infection upon intestinal smooth muscle function.Parasite Immunol. 1998; 20: 249-253Crossref PubMed Scopus (23) Google Scholar Later still in the evolution of the condition prostaglandins appear important because cyclooxygenase-2 inhibitors can diminish the enhanced neuromuscular activity.11Barbara G De Giorgio R Deng Y Vallance B Blennerhassett P Collins S.M Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice.Gastroenterology. 2001; 120: 1729-1736Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 12Swain M.G Blennerhassett P.A Collins S.M Impaired sympathetic nerve function in the inflamed rat intestine.Gastroenterology. 1991; 100: 675-682Abstract PubMed Google Scholar, 13Vallance B.A Collins S.M The effect of nematode infection upon intestinal smooth muscle function.Parasite Immunol. 1998; 20: 249-253Crossref PubMed Scopus (23) Google Scholar These changes in function are associated with changes in morphology. Damage to nerves is followed by remodeling and often is associated with hypertufting, which is associated with hypersensitivity in some models (e.g., dental abscess).14Byers M.R Taylor P.E Khayat B.G Kimberly C.L Effects of injury and inflammation on pulpal and periapical nerves.J Endod. 1990; 16: 78-84Abstract Full Text PDF PubMed Scopus (116) Google Scholar In inflammatory bowel disease (IBD), the morphology of the nerves is known to be abnormal, particularly in Crohn's disease, in which abnormal arborizing mucosal nerves expressing receptors for nerve growth factor have been reported.15Strobach R.S Ross A.H Markin R.S Zetterman R.K Linder J Neural patterns in inflammatory bowel disease an immunohistochemical survey.Mod Pathol. 1990; 3: 488-493PubMed Google Scholar During repair of tissue damage, in-growth of nerves is a vital part of the healing process. Nerve growth factors are overexpressed by fibroblasts, smooth muscle cells, and epithelial cells in response to inflammatory cytokines after tissue injury and are up-regulated in a range of inflammatory conditions such as chronic pancreatitis,16Friess H Zhu Z.W Di Mola F.F Kulli C Graber H.U Andren-Sandberg A et al.Nerve growth factor and its high affinity receptor in chronic pancreatitis.Ann Surg. 1999; 230: 615-624Crossref PubMed Scopus (150) Google Scholar experimental gastritis, IBD, and interstitial cystitis.17Lowe E.M Anand P Terenghi G Williams-Chestnut R.E Sinicropi D.V Osborne J.L Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis.Br J Urol. 1997; 79: 572-577Crossref PubMed Google Scholar Nerve growth factor regulates the expression of tachykinins and calcitonin gene-related peptides in sensory nerves and also the expression of VR118Priestley J.V Michael G.J Averill S Liu M Willmott N Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor.Can J Physiol Pharmacol. 2002; 80: 495-505Crossref PubMed Scopus (138) Google Scholar and purinergic receptor type 2X3,19Ramer M.S Bradbury E.J McMahon S.B Nerve growth factor induces P2X(3) expression in sensory neurons.J Neurochem. 2001; 77: 864-875Crossref PubMed Scopus (143) Google Scholar which may mediate postinflammatory hyperalgesia. Some neurotropic viruses such as the herpes virus target peripheral nerves and a specific cholinergic autonomic neuropathy has been shown after infection with the Epstein-Barr virus, suggesting direct toxicity. Indirect autoimmune mechanisms may be responsible for the acute ileus that can accompany the Guillain-Barré syndrome after C. jejuni infection. Dysphagia, with or without a dilated esophagus, is a common feature of Chagas' disease, a systemic disorder caused by infection with Trypanosome cruzi. Although plainly not a functional disorder, it shares several features with other disorders of esophageal motility, is useful to consider as the mechanism, is well understood, and follows an acute inflammatory lesion. Amastigotes spread throughout the body causing inflammatory lesions in cardiac, skeletal, and gastrointestinal smooth muscle. During the chronic phase, parasites are hard to detect and most of the damage appears to be caused by a T-lymphocyte-mediated neuronolysis.20Fernandez A Hontebeyrie M Said G Autonomic neuropathy and immunological abnormalities in Chagas' disease.Clin Auton Res. 1992; 2: 409-412Crossref PubMed Scopus (26) Google Scholar The damage to enteric nerves causes dilation of the hollow organs, most notably the colon and esophagus. Esophageal manometry shows a range of neuropathic features including multipeaked contraction and aperistalsis, with or without impaired relaxation of the lower esophageal sphincter.21de Oliveira R.B Rezende F.J Dantas R.O Iazigi N The spectrum of esophageal motor disorders in Chagas' disease.Am J Gastroenterol. 1995; 90: 1119-1124PubMed Google Scholar the mechanism of this impaired motility is unusual because it appears that circulating igg antibodies from patients with chagas' disease binds to m2-muscarinic acetylcholine receptors and shows agonist activity increasing smooth muscle tone.22Goin J.C Sterin-Borda L Bilder C.R Varrica L.M Iantorno G Rios M.C et al.Functional implications of circulating muscarinic cholinergic receptor autoantibodies in chagasic patients with achalasia.Gastroenterology. 1999; 117: 798-805Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar autoantibodies to ganglionic acetylcholine receptors also have been described in autoimmune autonomic neuropathies, half of which develop subacutely and often are associated with disordered gastrointestinal motility and a cholinergic deficit.23Klein C.M Vernino S Lennon V.A Sandroni P Fealey R.D Benrud-Larson L et al.The spectrum of autoimmune autonomic neuropathies.Ann Neurol. 2003; 53: 752-758Crossref PubMed Scopus (175) Google Scholar These findings have stimulated others to look for evidence of autoimmune damage to esophageal nerves in other esophageal disorders. Seven of 18 achalasic patients without Chagas' disease showed antineuronal antibodies24Verne G.N Sallustio J.E Eaker E.Y Anti-myenteric neuronal antibodies in patients with achalasia. A prospective study.Dig Dis Sci. 1997; 42: 307-313Crossref PubMed Scopus (101) Google Scholar; however, these autoantibodies also are found in reflux esophagitis,25Moses P.L Ellis L.M Anees M.R Ho W Rothstein R.I Meddings J.B et al.Antineuronal antibodies in idiopathic achalasia and gastro-oesophageal reflux disease.Gut. 2003; 52: 629-636Crossref PubMed Scopus (105) Google Scholar and are likely to be nonspecific, secondary to local inflammation. Acute onset of dyspeptic symptoms such as nausea and vomiting as a feature of infection is well recognized, but in most cases is short lived. Acute experimental infection with Norwalk and Hawaii viruses induces delayed gastric emptying, which also is observed after Rotavirus gastroenteritis,26Bardhan P.K Salam M.A Molla A.M Gastric emptying of liquid in children suffering from acute rotaviral gastroenteritis.Gut. 1992; 33: 26-29Crossref PubMed Scopus (30) Google Scholar but in most cases this rapidly resolves. The long-term effects are less well recognized and include 2 syndromes, postinfective gastroparesis and postinfectious dyspepsia, which may represent part of the spectrum of the same disorder. Because these are relatively rare consequences of infection, most studies are cross-sectional rather than prospective, which leads to potential bias in patient selection, emphasizing the contribution of anxiety, which often drives presentation to physicians. Typically, such patients form a rather small subgroup of patients with gastroparesis, 7 of 103 in a Mayo Clinic series published in 1990.27Oh J.J Kim C.H Gastroparesis after a presumed viral illness clinical and laboratory features and natural history.Mayo Clin Proc. 1990; 65: 636-642Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar They differ from other gastroparetic patients in being younger (mean age, 27 years) and present with a prodrome of fever, fatigue, and without diarrhea. Within a week of the resolution of the acute presumed viral illness, nausea, vomiting, and epigastric pain developed and gastric emptying studies showed a marked delay. This was associated with antral hypomotility. This also was reported in 10 children who developed gastroparesis after an acute viral illness, which in 8 children was shown to be caused by Rotavirus infection.28Sigurdsson L Flores A Putnam P.E Hyman P.E Di Lorenzo C Postviral gastroparesis presentation, treatment, and outcome.J Pediatr. 1997; 131: 751-754Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar Specific viruses associated with chronic postinfectious gastroparesis include cytomegalovirus,29Nowak T.V Goddard M Batteiger B Cummings O.W Evolution of acute cytomegalovirus gastritis to chronic gastrointestinal dysmotility in a nonimmunocompromised adult.Gastroenterology. 1999; 116: 953-958Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar herpes zoster,30Kebede D Barthel J.S Singh A Transient gastroparesis associated with cutaneous herpes zoster.Dig Dis Sci. 1987; 32: 318-322Crossref PubMed Scopus (30) Google Scholar and Epstein-Barr virus.31Bityutskiy L.P Soykan I McCallum R.W Viral gastroparesis a subgroup of idiopathic gastroparesis—clinical characteristics and long-term outcomes.Am J Gastroenterol. 1997; 92: 1501-1504PubMed Google Scholar, 32Vassallo M Camilleri M Caron B.L Low P.A Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis.Gastroenterology. 1991; 100: 252-258PubMed Google Scholar Several studies also have shown that patients infected with the human immunodeficiency virus have delayed emptying and an impaired antral response to feeding.33Konturek J.W Fischer H van dV I Domschke W Disturbed gastric motor activity in patients with human immunodeficiency virus infection.Scand J Gastroenterol. 1997; 32: 221-225Crossref PubMed Scopus (29) Google Scholar Although not strictly postinfectious, it is worth considering another acute gastroparetic syndrome that has been reported after vaccination. Symptoms developed within a few days of vaccination and were associated with delayed gastric emptying and antral hypomotility.34Pande H Lacy B.E Crowell M.D Inflammatory causes of gastroparesis report of five cases.Dig Dis Sci. 2002; 47: 2664-2668Crossref PubMed Scopus (24) Google Scholar The acute anorexia and vomiting associated with infections likely are caused by many factors including effects of inflammatory cytokines such as IL-1, IL-6, and tumor necrosis factor-α, serotonin, and prostaglandins, and in the case of bacterial enteritis, lipopolysaccharide. Most of these mediators activate vagal afferents to induce altered gastric motility but they also act via the circumventricular organs where the blood brain barrier is weak or absent (e.g., pineal gland, median eminence, neurohypophysis, area postrema, and the choroid plexus) to induce local cytokine production in the brain after binding to Toll-like receptor 4. Intracisternal IL-1 induces anorexia and delayed gastric emptying acting via hypothalamic and medullary sites. Because these effects can be blocked by indomethacin and corticotrophin-releasing factor antagonists, it seems likely that these effects are mediated via IL-1 stimulation of prostaglandin secretion, which in turn induces corticotrophin-releasing factor secretion, which potently inhibits gastric emptying.35Suto G Kiraly A Plourde V Tache Y Intravenous interleukin-1-beta-induced inhibition of gastric emptying involvement of central corticotrophin-releasing factor and prostaglandin pathways in rats.Digestion. 1996; 57: 135-140Crossref PubMed Scopus (31) Google Scholar An autonomic neuropathy was shown in 3 of 3 patients tested in the Mayo series27Oh J.J Kim C.H Gastroparesis after a presumed viral illness clinical and laboratory features and natural history.Mayo Clin Proc. 1990; 65: 636-642Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar and antral hypomotility also was shown in several series.27Oh J.J Kim C.H Gastroparesis after a presumed viral illness clinical and laboratory features and natural history.Mayo Clin Proc. 1990; 65: 636-642Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 34Pande H Lacy B.E Crowell M.D Inflammatory causes of gastroparesis report of five cases.Dig Dis Sci. 2002; 47: 2664-2668Crossref PubMed Scopus (24) Google Scholar The underlying pathology is rarely available, but in one individual who had an acute onset of vomiting 2 weeks after a flu-like illness who underwent surgery, mesenteric ganglionitis was reported. Full-thickness biopsy specimens of the stomach showed a marked T-lymphocyte infiltrate of the mesenteric plexus and a decrease in tachykinin immunoreactivity.36De Giorgio R Barbara G Stanghellini V Cogliandro R.F Arrigoni A Santini D et al.Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.Eur J Gastroenterol Hepatol. 2000; 12: 613-616Crossref PubMed Scopus (46) Google Scholar Cytomegalovirus has been detected in the myenteric plexus of an immunocompromised patient dying of cytomegalovirus infection whereas herpes zoster and human immunodeficiency virus37Griffin G.E Mill
Referência(s)