Aree anatomiche dello stomaco

Malattie gastriche e duodenali acido-correlate Gastrite Gastropatia Duodenite Ulcera gastrica Ulcera duodenale Inflammation of the stomach and duodenum can lead to ulceration. Gastritis and duodenitis and ulceration of the GI tract can produce a range of painful symptoms. Bleeding ulcers can be fatal.

Cause di gastrite, gastropatia e ulcera Infezione da Helicobacter pylori (H. pylori) Presente in ~80% dei paz con ulcera gastrica e 95% dei pazienti con ulcera duodenale Consumo regolare di FANS Uso di citostatici o steroidi Alcool, fumo e stress Ipersecrezione gastrica, ipergastrinemia, accelerato svuotamento gastrico Gastritis and peptic ulcer disease have a number of causes. The mucosa can be attacked by irritants (e.g. excess gastrin or acid, bacteria such as H. pylori, drugs such as NSAIDs, alcohol). Some individuals may be genetically predisposed to ulcer development. Calam & Baron, BMJ 2001; 323: 980–2.

Gastrite e gastropatia La gastrite è definita come un danno della mucosa gastrica associato alla presenza di infiltrato infiammatorio E’ causata nella grande maggioranza dei casi dall’H. pylori La gastropatia è un danno della mucosa gastrica in assenza di infiltrato infiammatorio E’ generalmente causata da agenti irritanti (FANS, alcool, bile)

Gastrite: classificazione di Sydney Criteri Endoscopici Localizzazione Pangastrite Gastrite del corpo Gastrite antrale Etiologia Autoimmune (tipo A) Da H. pylori (tipo B) Da farmaci o bile (tipo C) Severità Normale, bassa, media, alta Criteri istomorfologici Acuta Cronica Cronicamente attiva Gastritis may be classified by: endoscopic criteria (e.g. atrophic gastritis – see next slide) aetiology (e.g. bacteria related) localisation (e.g. antral) grading (low, middle, high) histomorphologic criteria (e.g. acute, chronic). Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

Classificazione di Sydney della gastrite

Gastrite antrale: endoscopia

Gastrite atrofica In atrophic gastritis, the mucosa shows signs of inflammation, is thinner and appears more transparent. Reproduced with permission. Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

Duodenite The nature of duodenitis is not completely understood. Duodenitis often is an unspecific reaction to duodenal ulceration. Endoscopy shows erythematous, erosive or nodular (pictured here) changes to the mucosa. Reproduced with permission. Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

Evoluzione della gastrite da Hp Gastrite cronica superficiale antrale Ulcera Duodenale Gastrite cronica estesa Ulcera gastrica Gastrite cronica atrofica K gastrico

Sintomi e segni della gastrite Pauci o asintomatica nella maggior parte dei casi Sindrome dispeptica (epigastralgia, ripienezza post-prandiale, senso di sazietà precoce, gonfiore epigastrico) Anemia Macrocitica da carenza di vit. B12 Microcitica da carenza di ferro

Terapia della gastrite da Hp Terapia eradicante raccomandata Se è interessato il corpo-fondo Se è presente gastrite atrofica Storia personale o familiare di K gastrico Terapia eradicante consigliata Se è presente sintomatologia dispeptica (20-30% di successo)

Infezione da H. pylori Gastrite Metaplasia gastrica Duodenite Malattia peptica (Ulcera gastrica e Ulcera duodenale) Cancro gastrico MALT Linfoma gastrico Twin studies have shown that host factors are important in determining the host response to H. pylori infection. Studies in humans have shown that duodenal ulcers are twice as common in blood group O non-secretors. Studies in mice have shown that different strains of mice developed different degrees of gastritis (e.g. severe vs hardly any gastritis) when infected with the same strain of H. pylori. It is likely that the genes involved in the inflammatory response determine progression to duodenal ulcer disease. Both duodenal and gastric ulcers are essentially gastric ulcers – these ulcers occur in gastric mucosa in the stomach or in gastric metaplasia mucosa in the duodenum. Calam & Baron, BMJ 2001; 323: 980–2.

Malattia peptica

Sintomatologia Dolore urente/gravativo in regione epigastrica Nausea Calo ponderale Anoressia Astenia Peptic ulcers give rise to a number of symptoms, which can be severely debilitating to the patient.

Ulcera peptica in fase acuta Epithelial lesions extending through the muscularis mucosae into the submucosa, are defined as ulcers. This ulcer takes the form of a deep mucosal lesion surrounded by a smooth mound, located at the angularis. Reproduced with permission. Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

Ulcera duodenale This view shows a longish duodenal ulcer at the ventral wall of the bulb with regular, rounded edges above and an ulcer base below the normal mucosal surface. The ulcer base is flat and partly covered by fibrin. Reproduced with permission. Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

PATOGENESI DELL’ULCERA DUODENALE Predisposizione genetica Antrite da ( > massa cell. parietali ) Helicobacter pylori Gastrina Somatostatina Secrezione acida Carico acido in duodeno Metaplasia gastrica in duodeno Altri fattori Duodenite Ulcera duodenale

Diagnosi Anamnesi Endoscopia Ricerca H. pylori Uso di FANS Pazienti >45 anni Pazienti con sintomi di allarme Storia personale di ulcera gastrica Storia familiare di K gastrico o altri fattori di rischio neoplastico Ricerca H. pylori Peptic ulcers are diagnosed using a combination of history, endoscopy and H. pylori testing. Symptoms cannot be used to accurately diagnose PUD, as classic ulcer symptoms often occur in patients with functional dyspepsia, and many ulcer patients have atypical symptoms. Endoscopy is the test of choice to exclude chronic peptic ulcers, but these can now be inferred by indirect testing. H. pylori causes 90% of duodenal ulcers and 70% of gastric ulcers; aspirin and NSAID use account for the bulk of the remainder. Patients who are not infected with H. pylori and not taking NSAIDs have a low likelihood of ulcer disease. Talley et al., BMJ 2001; 323: 1294–7.

Differenze tra UG e UD UG UD Rara prima dei 40 aa Dolore spesso esacerbato dal cibo e alleviato dal digiuno Secrezione acida normale Calo ponderale possibile Ematemesi più frequente della melena UD La maggior parte colpisce tra I 25 e I 75 aa Dolore alleviato dal cibo e dagli antiacidi, spesso notturno Secrezione acida aumentata Calo ponderale raro Melena più frequente dell’ematemesi The typical gastric ulcer patient will be older than 40 years. Their pain is likely to worsen on eating, their acid secretion is normal, they may have lost weight and vomited blood. The typical duodenal ulcer patient will be aged 50–60 years. Their pain is reduced by eating and the administration of antacids, but is bad at night. Their acid secretion is increased, they are unlikely to have lost weight, and may pass blood in their stools.

Complicanze della malattia peptica Emorragia Causata dalla erosione di un vaso sanguigno; potenzialmente letale Perforazione Provoca dolore improvviso e violento; richiede immediato ricovero ed intervento chirurgico Stenosi Cicatriziale, può impedire lo svuotamento gasrico. Caratterizzata da vomito continuo e perdita di peso The potential complications of peptic ulcer disease include bleeding, perforation and obstruction. Haemorrhage occurs in 15–20% of cases. Perforation occurs in approximately 5% of cases. Obstruction occurs in approximately 2% of cases. These complications are usually serious and sometimes fatal. Vaira et al., Gastroenterol 1997; 113(Suppl 6): S78–84.

Ulcera gastrica in fase di sanguinamento Endoscopic investigation of a 71-year-old man with haematemesis revealed a 2 cm ulcer with pulsatile, arterial bleeding. Control of bleeding was achieved by injecting the vessel with epinephrine, followed by bipolar electrocautery. Reproduced with permission. Martin & Lyons, The Atlas of Gastrointestinal Endoscopy. http://www.mindspring.com/~dmmmd/atlas_1.html

Ulcera duodenale sanguinante In this duodenal ulcer at the left edge of the figure, there is an oozing, active bleeding. According to the Forrest classification of gastrointestinal haemorrhage of the upper GI tract, this bleeding is graded as Forrest Ib. Reproduced with permission. Freytag et al., Atlas of Gastroenterological Endoscopy. www.endoskopischer-atlas.de/indexe.htm

L’emorragia da ulcera Si verifica nel 15–20% dei pazienti ulcerosi1 Le ulcere peptiche rappresentano la principale causa di emorragia del tratto digestivo superiore (con mortalità di circa il 10%)2 Rischio per UG: 25% circa Rischio per UD: 50%circa The commonest cause of upper GI bleeding is peptic ulcer. Severe bleeding is due to erosion of an artery by an ulcer. The severity of bleeding depends on the site of the ulcer and the size of the defect in the artery; bleeding from a defect >1 mm is unlikely to stop spontaneously. Large ulcers arising at the posterior part of the duodenal cap may erode the gastroduodenal artery and result in particularly severe bleeding. Bleeding-related mortality is about 10%. In many cases, bleeding is associated with NSAID use. 1. Vaira et al., Gastroenterol 1997; 113(Suppl 6): 78–84. 2. Dallal & Palmer, BMJ 2001; 323: 115–17.

Sintomi e segni di emorragia Melena – feci picee Ematemesi – vomito ematico o a posa di caffè Segni Tachicardia Pallore Sudorazione Estremità fredde Sincope Senso di mancamento Confusione mentale The symptoms of an acute bleeding ulcer include melaena and haematemesis; patients who present with haematemesis tend to have more severe bleeding than those who present with melaena. These symptoms are often accompanied by other signs. The symptoms of an acute bleeding ulcer differ from those of a chronic bleeding ulcer (see later slides).

Obiettivi terapeutici nella malattia peptica Risoluzione della sintomatologia Guarigione della lesione Prevenzione delle recidive Prevenzione delle complicanze Goals of treatment in PUD include: pain relief and resolution of symptoms mucosal healing prevention of recurrence and complications.

Helicobacter pylori (H. pylori)

Prevalenza dell’ H. pylori nella malattia peptica Prevalenza di H. pylori nelle ulcere sanguinanti Prevalenza di H. pylori nelle ulcere non sanguinanti 100 80 60 Prevalenza (%) 40 H. pylori is strongly associated with PUD and eradication therapy can ‘cure’ the condition. There is substantial geographical variation in H. pylori prevalence. Increasingly, however, clinicians are seeing H. pylori-negative ulcers. Modified from Vaira et al., Gastroenterology 1997; 113(Suppl 6): S78–84. 20 Germany Italia Hong Spain USA Hong Denmark Taiwan Germany Turkey Kong Kong Vaira et al., Gastroenterol 1997; 113(Suppl 6): S78–84.

Fattori di rischio per l’infezione da H. pylori Età Infezione in precoce età nei paesi in via di sviluppo Nazione Tassi più elevati nei paesi in via di sviluppo Reddito Inversamente correlato con I tassi di infezione Sesso Incidenza simile Fattori familiari Familiarità? Trasmissione oro-orale o oro-fecale tra conviventi? Alcool Rischio non aumentato Gruppo sanguigno Nessuna associazione Fumo Logan & Walker, BMJ 2001; 323: 920–2. Report of the Digestive Health Initiative, Gastroenterol 1997; 113: S4–8.

Patogenesi del danno da Hp Batterio Gram-negativo spiraliforme Fattori di colonizzazione: ureasi, motilità, adesine Liberazione di enzimi (ureasi, fosfolipasi, proteasi) e tossine (vacuolizzante e CagA) Flogosi e stimolo antigenico

Diagnosi dell’infezione da H. pylori

Test diagnostici Non-invasivi Invasivi Ricerca degli anticorpi nel siero C13 Urea breath test Ricerca degli antigeni nelle feci Invasivi Test rapido all’ureasi Istologia Coltura The presence of H. pylori can be confirmed using non-invasive (non-endoscopic) and invasive (endoscopic) diagnostic tests. H. pylori elicits a local mucosal and systemic antibody response that can be detected by ELISA antibody or latex agglutination tests. As antibody titre falls only slowly after eradication, antibody detection cannot be used to determine H. pylori eradication or to measure reinfection. Simple finger-prick antibody tests are used in primary care. The 13C-urea breath test can be used in primary care, but the 14C-urea breath test is radioactive and cannot. Biopsy-based methods are liable to sampling error as infection is patchy. Multiple biopsy specimens are needed for this reason. Urease tests include the CLO test. Logan & Walker, BMJ 2001; 323: 920–2.

C13 Urea Breath Test

C13 Urea Breath Test

Test rapido all’ureasi

Test consigliati nella pratica clinica Paziente Asintomatico Dispepsia saltuaria, <50 anni, nessun sintomo di allarme Sintomi persistenti, >50 anni o sintomi di allarme Test Non raccomandato Non invasivo Invasivo Not all patients need to be tested for H. pylori. Testing is not recommended in asymptomatic patients. Non-invasive testing is recommended in young patients, and those with frequent dyspepsia but no alarm symptoms. Invasive testing is recommended in older patients, and those with persistent symptoms and alarm symptoms. Testing should only be conducted if there is an intention to treat the condition if H. pylori is confirmed. Report of Digestive Health Initiative, Gastroenterol 1997; 113: S4–8.

Terapia delle ulcere H. pylori-positive

Farmaci utilizzati nei regimi di eradicazione dell’infezione da H Farmaci utilizzati nei regimi di eradicazione dell’infezione da H. pylori PPI Ranitidina bismuto citrato (RBC) Amoxicillina Macrolidi (es. claritromicina) Nitroimidazoli (es. metronidazolo) Tetraciclina Bismuto Agents used most often in anti-H. pylori regimens include PPIs, ranitidine bismuth citrate, bismuth and antibiotics. These agents are combined as ‘triple therapy’ or ‘quadruple therapy’. Therapy is usually administered for 7–14 days. Gisbert et al., Curr Opin Gastroenterol 2001; 17(Suppl 1): S47–54.

Sequenza delle terapie eradicanti Maastricht 2–2000 PPI x 2 + tinidazolo 500 mg x 2 + levofloxacina 500 mg + tetraciclina 500 mg x 4 + amoxicillina 1 g x 2 + claritromicina 500 mg x 2 PPI x 2 (o RBC) + bismuto 120 mg x 4 + claritromicina 250 mg x 2 Terapia di terza linea per 1 settimana + metronidazolo 500 mg x 2 PPI x 2 Terapia di riserva (quadruplice terapia) per 1 settimana PPI x 2 (o RBC) Oppure Terapia di prima scelta (tripice terapia) per 1 settimana First-line therapy for H. pylori eradication consists of triple therapy with a PPI or RBC plus two antibiotics. However, first-line therapies fail to eradicate H. pylori in some patients, necessitating the use of second- and sometimes even third-line therapies. Second-line therapy is ‘quadruple therapy’ – PPI (or RBC) plus bismuth, plus two antibiotics. RBC = ranitidina bismuto citrato Pilotto & O’Morain, Curr Opin Gastroenterol 2000; 16(Suppl 1): S44–51. Bazzoli, Eur J Gastroenterol Hepatol 2001; 13(Suppl 2): S3–7.

Efficacia della triplice terapia nell’ eradicazione dell’ H. pylori 100 92.4 93.8 85.7 Intention to treat Per protocol 83.1 80 LAN: lansoprazolo CLA: claritromicina AMO: amoxicillina MET: metronidazolo Eradicazione (%) 60 40 Lansoprazole-based triple therapy regimens have shown considerable efficacy for H. pylori eradication. Eradication rates of 85.7% (per protocol analysis) and 83% (intent to treat analysis) were observed with a regimen consisting of lansoprazole, clarithromycin and amoxicillin. Better eradication rates of 93.8% (per protocol analysis) and 92.4% (intent to treat analysis) were observed with a regimen consisting of lansoprazole, clarithromycin and metronidazole, even by using only 50% of the dose of lansoprazole and clarithromycin compared to the other regimen. Tolerability was also better with a low dose plus metronidazole regimen. 20 LAN 30 mg bd CLA 500 mg bd AMO 1 g bd (n=63) LAN 30 mg od CLA 250 mg bd MET 500 mg bd (n=65) Bazzoli et al., Aliment Pharmacol Ther 2002; 16: 153–8.

Influenza dell’eradicazione sulla guarigione dell’ulcera ***95 ** 88 H. pylori eradicato H. pylori non eradicato 100 76 73 **p<0.01 ***p<0.001 Guarigione (%) A review of data from more than 4000 patients in 60 trials revealed that ulcer healing was positively influenced by the successful eradication of H. pylori. Healing rates of 95% in duodenal ulcer and 88% in gastric ulcer were observed in patients in whom H. pylori was eradicated. These healing rates were significantly higher than those observed in patients in whom H. pylori persisted. Healing rates of 76% in duodenal ulcer and 73% in gastric ulcer were observed in patients in whom H. pylori persisted. Ulcera duodenale Ulcera gastrica Treiber & Lambert, Gastroenterol 1998; 93: 1080–4.

L’eradicazione riduce le recidive dell’ulcera gastrica 100 Non-eradicati Eradicati 80 60 Recidive di UG (%) 40 A review of data from five studies revealed that recurrence of gastric ulcer is reduced by eradication of H. pylori. Labenz & Borsch (1): omeprazole, omeprazole/ciprofloxacin, omeprazole/amoxicillin, and omeprazole/roxithromycin Sung et al.: omeprazole Labenz & Borsch (2): omeprazole, omeprazole/amoxicillin, omeprazole/ciprofloxacin, and bismuth-containing medication/metronidazole/tetracycline/ranitidine Karita et al.: plaunotol/metronidazole/amoxicillin Seppälä et al.: bismuth-containing medication, ranitidine and bismuth-containing medication/metronidazole Reproduced with permission. 20 Labenz Sung Labenz Karita Seppälä & Borsch et al. & Borsch et al. et al. (n=11) (n=19) (n=18) (n=4) (n=42) Labenz Sung Labenz Karita Seppälä & Borsch et al. & Borsch et al. et al. (n=16) (n=26) (n=32) (n=26) (n=10) Hopkins et al., Gastroenterol 1996; 110: 1244–52.

L’eradicazione riduce notevolmente le recidive di ulcera duodenale H. pylori + vi H. pylori – vi *** 95 *** 96 *** 95 *** 92 100 58 Pazienti in remissione (%) 40 30 Meta-analysis of 126 articles documenting duodenal ulcer recurrence from 1984–1995 revealed that recurrence of duodenal ulcer is markedly reduced by eradication of H. pylori. A significantly greater proportion of patients in whom H. pylori was eradicated remained ulcer free at 6, 12, 18 and 24 months compared with patients in whom eradication of H. pylori was unsuccessful. 92–96% of patients in whom H. pylori was eradicated were ulcer free at 6–24 months. In patients in whom eradication of H. pylori was unsuccessful, ulcer recurrence occurs in an increasing proportion over time; <60% of these patients are ulcer free at 6 months and only 25% are ulcer free at 24 months. 25 Mesi 6 12 18 24 ***p<0.001 Huang et al., Am J Gastroenterol 1996, 91: 1914.

Test post-eradicazione E’ consigliabile fare un test dopo la terapia Utilizzare test di infezione attiva: non utile la sierologia UBT è il test di prima scelta La persistenza dei sintomi non significa fallita eradicazione There is a movement towards routine testing for the presence of H. pylori following eradication therapy. The best test to confirm eradication is the 13C-UBT. As antibody titre reduces only slowly after eradication, antibody-based tests are not helpful to test for H. pylori eradication. Persistent symptoms after documented H. pylori eradication are often due to GORD. Nakajima et al., Curr Pharm Des 2000; 6: 1515–29. Malaty, Paediatr Drugs 2000; 2: 357–65. Harris & Misiewicz, BMJ 2001; 323: 1047–50.

Cause di fallimento della terapia Resistenza agli antibiotici Mancata compliance Regime di terapia inadeguato Severità della malattia Fumo Area geografica H. pylori eradication therapy can fail for a number of reasons, not all of which are related to the efficacy of the treatment regimen. Pilotto & O’Morain, Curr Opin Gastroenterol 2000; 16(Suppl 1): S11–18. Harris & Misiewicz, BMJ 2001; 323: 1047–50. Perri et al., Aliment Pharmacol Ther 2001; 15: 1023–9. Pilotto, Drugs Aging 2001; 18: 487–94.

Ulcera peptica H. pylori-negativa

Incremento di ulcere H. pylori-negative nel 1995–2000 13% 33% The proportion of ulcers not associated with H. pylori is increasing. Between 1995 and 2000, there was a significant increase in the proportion of H. pylori-negative ulcers (p<0.01). Between 1995 and 2000, there was a significant decrease in the proportion of H. pylori-positive ulcers (p<0.05). 87% 67% H. pylori-negative H. pylori-positive Juhasz, Gut 2001; 49: A64.

Possibili cause di ulcere Hp negative Uso di fANS Rischio aumentato di 3-5 volte Falsi-negativi ai test diagnostici Pregressa terapia antibiotica o antisecretoria Ipersecrezione acida gastrica Altre infezioni The cause of H. pylori-negative duodenal ulcers may be multifactorial. These ulcers may have an aggressive clinical course and can be refractory to treatment. NSAID use may be covert – many patients take OTC NSAIDs and other pain-relief drugs. Other, uncommon causes of H. pylori-negative ulcers include Crohn’s disease and Zollinger-Ellison syndrome. Freston, Aliment Pharmacol Ther 2001; 15(Suppl 2): 2–5. Harris & Misiewicz, BMJ 2001; 323:1047–50.

Ulcere da FANS

H. pylori, FANS e rischio di ulcera peptica Entrambi aumentano indipendentemente e significativamnete il rischio di ulcera peptica e di emorragia Hanno un’azione sinergica sulla comparsa di ulcera e di sanguinamento A meta-analysis was used to investigate the relationship between H. pylori infection and the use of NSAIDs in the pathogenesis of PUD. Huang et al., Lancet 2002; 359: 14–22.

Trattamento delle ulcere Hp negative e non legate all’uso di FANS Maastricht 2-2000 Consensus Assicurarsi che l’infezione sia realmente assente (eseguendo diversi test, compresa la sierologia), e poi eseguire test (gastrinemia ed esame del succo gastrico) per escludere la sindrome di Zollinger-Ellison Eseguire biopsie multiple sia su UG che su UD e trattare con antisecretori The majority of ulcers are H. pylori positive or NSAID-positive. In cases where patients are proven H. pylori-negative or NSAID-negative, it is important to exclude all other disease and then to treat empirically with antisecretory therapy. Malfertheiner et al., Aliment Pharmacol Ther 2002; 16: 167–80.

Patogenesi delle ulcere da FANS FATTORI PROTETTIVI FATTORI AGGRESSIVI Prostaglandine Acido + pepsina H. pylori Strato di muco Bicarbonato Cellule dell’epitelio di superficie In the healthy GI tract, the mucosa and blood supply are shielded from aggressive factors (e.g. acid, pepsin and H. pylori) by a number of protective factors, including bicarbonate (secreted by the surface epithelial cells) and a layer of mucus. These protective factors are maintained by prostaglandins. Flusso ematico Seager & Hawkey, BMJ 2001; 323: 1236–9.

Patogenesi delle ulcere da FANS FATTORI PROTETTIVI FATTORI AGGRESSIVI + Prostaglandine FANS Acido + pepsina H. pylori Strato di muco Bicarbonato Cellule dell’epitelio di superficie NSAIDs block the production of prostaglandins. This triggers a cascade of events. Flusso ematico Seager & Hawkey, BMJ 2001; 323: 1236–9.

Patogenesi delle ulcere da FANS FATTORI PROTETTIVI FATTORI AGGRESSIVI + Prostaglandine FANS Acido + pepsina H. pylori Strato di muco Bicarbonato Surface epithelial cells begin to atrophy. Epitelio di superficie Flusso ematico Seager & Hawkey, BMJ 2001; 323: 1236–9.

Gastropatia da FANS E’ la più comune forma di tossicità grave da farmaci accertata1 Dispepsia compare nel 15% dei pazienti2 Prevalenza di ulcere: 15–311 Maggiior rischio di UG che di UD3,4 Rischio di complicanze aumentato 4 volte4 Emorragia: 3.091 Perforazione: 5.931 Morte: 7.621 NSAID gastropathy has far-reaching effects, resulting in dyspepsia and ulceration and GI complications. 1. Sung et al., J Gastroenterol Hepatol 2000; 15: G58–68. 2. Larkai et al., J Clin Gastroenterol 1989; 11: 158–62. 3. Graham et al., Ann Intern Med 1993; 119: 257–62. 4. Hawkey, Gastroenterol 2000; 119: 521–35.

Pazienti ad alto rischio di complicanze associate all’uso di FANS Età >65 anni Storia di ulcera Terapia concomitante con: aspirina corticosteroidi anticoagulanti Dosi elevate Alcool, fumo Sesso maschile Singh et al., J Rheumatol 1999; 26(Suppl 56): 18-24. Larkai et al., J Clin Gastroenterol 1989; 11: 158–62. Graham et al., Ann Intern Med 1993; 119: 257–62. Hawkey, Gastroenterol 2000; 119: 521–35.

Terapia dell’ulcera da FANS Sopsensione o sostituzione con agenti meno lesivi Soppressione della secrezione acida PPI Anti-H2 ad alte dosi Citoprotettivi Misoprostol (effetti collaterali seri) NSAID-induced peptic ulcers are, ideally, managed by removal of the causative factor (the NSAID) and suppression of acid secretion, to allow healing. NSAIDs can be replaced with less toxic agents such as COX-2 inhibitors. The use of mucosal protective agents (e.g. the prostaglandin E1 analogue, misoprostol) does prevent gastric injury by NSAIDs, but causes GI side effects at the doses needed to protect against NSAID-induced ulcers. Acid suppression with normal-dose PPIs or high-dose H2RAs is effective. Seager & Hawkey, BMJ 2001; 323: 1236–9. Silverstein et al., Ann Intern Med 1995; 123: 241–9. Graham et al., Ann Intern Med 1993; 119: 257–62. Yeomans et al., N Engl J Med 1998; 338: 719–26.