Von Bulut et al. wird über einen 30 Jahre alten Patienten berichtet, der unter der Diagnose „M. Crohn des Dünndarms“ 4 Jahre lang mit Azathioprin behandelt worden war [1]. Nachdem es zu Gewichtsverlust, Diarrhö und Fieber gekommen war, der Patient anämisch war, die Albuminkonzentration im Serum erniedrigt und eine Stuhluntersuchung auf pathogene Keime negativ, wurde eine immunsuppressive Therapie mit Prednison-Stoß und Ustekinumab begonnen, bis nach weiterer klinischer Verschlechterung bei der Endoskopie in der Duodenalmukosa histologisch und mittels PCR ein M. Whipple nachgewiesen wurde. Trotz einer nun begonnenen antibiotischenTherapie mit Ceftriaxon und Meropenem verstarb der Patient immunsupprimiert an den Folgen von Candida-Sepsis und Hepatitis-E-VirusInfektion. Als „Message“ der Veröffentlichung wird dieser tragische Verlauf als Komplikation einer Infektion mit T. whipplei bei vorbestehendem Morbus Crohn interpretiert. Dies wäre tatsächlich eine Erstbeschreibung. Tatsächlich aber ist viel wahrscheinlicher, dass es sich bei dem jungen Mann von Beginn an um einen M. Whipple mit vorwiegend enteraler Manifestation gehandelt hat. Es wird im Fallbericht nicht mitgeteilt, ob anfänglich, während oder nach den 4 Jahren der immunsuppressiven Behandlung die Dünndarmschleimhaut auf eine Infektion durch T. whipplei untersucht worden ist. Unter der Immunsuppression war im Einklang mit der sich verschlimmernden klinischen Situation eine Progression der Infektion zu erwarten, sodass spätestens nach 4 Jahren der Immunsuppression vermutlich jede Biopsie aus der Dünndarmschleimhaut die Infektion aufgezeigt hätte, selbst wenn eine Biopsie möglicherweise 4 Jahre zuvor wegen fleckförmigen Befalls negativ gewesen sein sollte. Leider ist eine jahrelange Latenz zwischen dem Auftreten der M. WhippleSymptomatik und dem Nachweis der Infektion keine Seltenheit. In einer klinischen Studie haben wir jüngst in einer Fragebogenaktion bei 40 Patienten mit M. Whipple mit primär rheumatischer Manifestation nach der Zeitdauer zwischen dem Beginn der Symptomatik und der Diagnose gefragt. 24 Patienten haben diese Frage beantwortet: Die mittlere Latenz war 7 ± 4,5 Jahre (M ± SD) bei einer Streuung von 0 bis 15 Jahren [2]. In einer früheren, mehr kasuistischen Veröffentlichung hatten wir in einer Kohorte über 15 Patienten mit M. Whipple berichtet [3], bei welchen die längste Zeit bis zur Diagnose 13 Jahre bei Patient Nr. 4 dauerte, der mit Steroiden und Infliximab behandelt worden war, wegen IRIS bei M. Whipple auf dem rechten Auge blind, eine Dünndarmperforation überlebte. Patient Nr. 7 mit M. Whipple hatte innerhalb von 8 Jahren die größte Anzahl von Immunsuppressiva erhalten, nämlich: Glukocorticoide, Gold, Methothrexat, Leflunomid, Cyclophosphamid, Infliximab, Etarnecept, Cyclosporin und eine Radiosynoviorthese. Die Frage, wie hoch die Dunkelziffer dieser immunsuppressiv behandelten M. Whipple-Patienten mit tödlichem Ausgang ist, bleibt unbekannt, denn bei der Fragebogenaktion [2] konnten naturgemäß nur diejenigen befragt werden, die bis dahin nicht verstorben waren und bei der Kohortenstudie [3] waren 45 von 107 Patienten „lost during follow-up“. Aus unseren Unterlagen zu mehr als 300 Patienten mit M. Whipple geht hervor, dass ein tödliches Ende mit Candida-Sepsis bei den durch die Infektion mit T. whipplei plus durch ärztlich verordnete Immunsuppression hochgradig immungeschwächten Patienten mit M. Whipple nicht untypisch ist. Die Publikation von Bulut gibt Gelegenheit, auch die Gastroenterologen auf diese finstere Seite der Medizin hinzuweisen. Sie wäre nicht an die Öffentlichkeit gelangt, hätten die 5 Autoren der Kasuistik nicht die Idee gehabt, den M. Whipple als „eine seltene und herausfordernde Komplikation in einem Patienten mit M. Crohn“ zu veröffentlichen [1]. Autorinnen/Autoren

We examined fecal specimens of patients with diarrhea from 3 continents for Tropheryma whipplei and enteropathogens. T. whipplei was most common in South Africa, followed by Singapore and Germany. Its presence was associated with the presence of other pathogens. An independent causative role in diarrhea appears unlikely.

Most patients with Whipple’s disease have rheumatic symptoms. The aim of our prospective, questionnaire-based, non-interventional clinical study was to assess whether these symptoms are useful in guiding the differential diagnosis to the rheumatic disorders. Forty patients with Whipple’s disease, followed by 20 patients for validation and 30 patients with rheumatoid-, 21 with psoriatic-, 15 with palindromic- and 25 with axial spondyloarthritis were recruited for the present investigation. Patients with Whipple’s disease and patients with rheumatic disorders were asked to record rheumatic symptoms on pseudonymized questionnaires. The data obtained were subjected to multiple logistic regression analysis. Episodic pain with rapid onset, springing from joint to joint was most common in patients with palindromic arthritis and second most common and somewhat less conspicuous in Whipple’s disease. Continuous pain in the same joints predominated in patients with rheumatoid-, psoriatic-, and axial spondyloarthritis. Multiple logistic equations resulted in a predicted probability for the diagnosis of Whipple’s disease of 43.4 ± 0.19% (M ± SD) versus a significantly lower probability of 23.8 ± 0.19% (M ± SD) in the aggregate of patients with rheumatic disorders. Mean area under the curve (AUC) ± SD was 0.781 ± 0.044, 95% CI 0.695–0.867, asymptotic significance p < 0.001. The logistic equations predicted probability for the diagnosis of Whipple’s disease in the initial series of 40 patients of 43.4 ± 0.19% was not significantly different in the subsequent 20 patients of 38.2 ± 0.28% (M ± SD) (p = 0.376). The data may be useful in a predictive algorithm for diagnosing Whipple’s disease. The project is registered as clinical study DRK S0001566.

Intercostal Nerve Course DifferentI would like to thank the authors for their very interesting article (1).Since, according to the literature, abdominal pain originates from the abdominal wall in 2% to 30% of cases, attention should once again be paid the intercostal nerves.However, the actual course of the intercostal nerves in this area differs significantly from that depicted in the figure .The intercostal nerves run, coming from dorsal cranial and descending in a ventral caudal direction between the internal oblique and the transverse abdominal muscle.They penetrate the rectus sheath obliquely and then lie within the rectus sheath lateral to the rectus abdominis muscle.Their direction does not change during this passage.Since the intercostal nerves are enveloped by a tunnel of firm connective tissue during their oblique path through the rectus sheath, this is the site where nerve compression may occur.Within the rectus sheath, the intercostal nerves first run between the rectus abdominis muscle and the posterior lamina of the rectus sheath.In most cases, they split into a medial and a lateral branch before they enter the rectus abdominis muscle from dorsal at an angle, then pass through it obliquely while innervating it, then exit it on it is anterior surface to finally penetrate through the anterior lamina of the rectus sheath.I think compression at the exit points are less relevant.If this happened, skin nerves would then also be compressed at other sites of the body, resulting in superficial pain.However, this course of the intercostal nerve does not make any difference to the symptoms described in the article.Nevertheless, I think it is of help to present the anatomical background information correctly.

Whipple’s disease (WD) is a rare systemic condition caused, in genetically predisposed subjects, by Tropheryma whipplei, a common bacterium widespread in the environment. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and DQB1*06 and by the demonstration that, in patients with WD, the cytokine genetic profile is skewed toward a Th2 and Treg response. Since IL-16 is involved in hampering the development of a protective macrophagic response against Tropheryma whipplei, we investigated whether the genetic background of IL-16 is different between patients with WD and controls. The −295 T-to-C polymorphism of the promoter region of the IL-16 gene was studied in 90 patients with WD and 152 healthy controls. Levels of serum IL-16 protein were also tested. The frequency of the wild type T allele was significantly higher in patients with WD compared to the controls (155/180 vs. 235/304; p = 0.02 for the Chi2 test), odds ratio 1.82 [95 % confidence interval (CI) 1.07–3.10]. The TT genotype was found in 65/90 patients with WD and 88/152 controls (p = 0.026). No relationship was found between serum levels of IL-16 and genotypes. Although the functional consequences of this genetic background on levels of IL-16 and on the course of the disease are still unknown, we found, for the first time, that the wild type T allele and the TT genotype of the −295 polymorphism are associated with WD.

Background: There is no agreement on how and for how long Whipple's disease should be treated. In a randomized trial it was shown that patients can be cured with ceftriax-one or meropenem followed by trimethoprim-sulfamethoxazole for 12 months. The present study tested whether trimethoprim-sulfamethoxazole for three months is sufficient.Methods: In the time from July 2004 to July 2008, 40 untreated patients from central Europe were sequentially admitted to an open-label, non-randomized extension of the previous trial with essentially an identical protocol. The modified treatment consisted of 2 g ceftriaxone intravenously once daily for 14 days followed by oral trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 months.Primary endpoint was treatment efficacy compared with the previous study.Results: Twelve months of treatment with trimethoprim-sulfamethoxazole was not more effective than 3 months as indicated by clinical findings, laboratory (p = 0.405, p = 0.631, resp.), and histological data (p = 0.456). 36 of 37 surviving patients including 14 with cerebrospinal infection were in remission without evidence of recurrence after a median follow-up time of 80 months. In one patient, Tropheryma whipplei arthritis recurred 63 months after initial therapy. Secondary endpoints indicate that histology of intestinal biopsies was a more useful indicator to determine eradication of T. whipplei than PCR. In submucosal and extra-intestinal tissue, the diagnostic value of the PCR was superior. Prospective data disclosed a heterogeneous spectrum of clinical presentation and course of Whipple's disease.Conclusion: This study indicates that ceftriaxone followed by three months of trimethoprim-sulfamethoxazole is highly efficacious in the treatment of Whipple's disease. Trial registration: ISRCTN45658456 (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

During antimicrobial treatment of classic Whipple’s disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4+ T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3+, predominantly CD45RO+CD4+ T cells. In the periphery, initial reduction of CD4+ cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4+ T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4+ T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei–specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4+ T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

Sir, Whipple’s disease is a chronic infection caused by Tropheryma whipplei. In a prospective study, the CNS was found to be involved in 38.5% of the cases. Treatment is not always successful. – 6 Co-trimoxazole (trimethoprim/sulfamethoxazole) has been reported to be significantly more effective than tetracycline; however, resistance to co-trimoxazole has also been observed. – 6 More recently, there have even been reports describing resistance of CNS infections to treatment with ceftriaxone, a bactericidal antibiotic penetrating the blood–brain barrier. In 2002, a patient presented with diarrhoea, weight loss to 64 kg, anaemia (8.4 g/dL haemoglobin) and erythrocyte sedimentation rate of 33 mm/h. The medical history revealed relapsing arthritis since 1991 and pericarditis necessitating pericardial resection in 1993. Gastrointestinal biopsies disclosed periodic acid-Schiff (PAS)-positive macrophages typical of untreated Whipple’s disease in the mucosa of the duodenum and the ileum and in the submucosa of the colon. The patient had no cerebral symptoms. However, microscopic examination of centrifuged CSF obtained by spinal puncture showed a PAS-positive macrophage typical of Whipple’s disease (histopathology carried out by Dr Reinhard Golz, Wuppertal), and the PCR to T. whipplei in the CSF was positive. The patient was admitted to a prospective treatment trial, as reported in Feurle et al. He was randomized to 2 g of ceftriaxone infused intravenously once daily for 2 weeks, followed by oral co-trimoxazole at a dosage of 160/300 mg twice daily for 12 months. While the patient recovered from all signs and symptoms of Whipple’s disease, the PCR for T. whipplei remained positive in the CSF for 5.5 years despite additional treatment with 1 g of meropenem infused intravenously thrice daily for 2 weeks followed by cotrimoxazole for another year. After a further year of cotrimoxazole, the CSF was still positive in the T. whipplei PCR, while the patient was receiving this treatment. PAS-positive macrophages in duodenal mucosal biopsies and in the CSF had disappeared. CT and magnetic resonance imaging of the brain did not reveal any structural abnormality. At this time, the patient had no symptoms of systemic or cerebral Whipple’s disease. The presence of T. whipplei in the CSF was confirmed by sequence analysis of the amplification product, and the viability was established by culture in MRC5 fibroblasts and in axenic medium. In vitro susceptibility of the cultured strain to ceftriaxone, meropenem, tetracyclines and co-trimoxazole is shown in Table 1. The risk of this patient developing symptomatic cerebral disease seemed unpredictable. After obtaining written informed consent for an individual treatment attempt, this patient was treated with chloroquine and tetracycline, a combination suggested previously. Chloroquine (or hydroxychloroquine) enhances antimicrobial activity of tetracyclines by raising the pH of the phagolysosomes within macrophages. Minocycline was selected as the tetracycline in this case as this compound has been reported to cross the blood–brain barrier well. Pollock et al., taking advantage of this pharmacokinetic property, were probably the first to treat a patient with cerebral Whipple’s disease with minocycline. They did not combine it with chloroquine. Others prefer the combination of doxycycline and chloroquine. In the present study, the dosage of chloroquine, based on a body weight of 83 kg, was 1725 mg of chloroquine phosphate in divided doses orally on day 1, and 575 mg on the second to the fourth day, followed by one 250 mg chloroquine phosphate tablet once daily for 45 days. A serum concentration of 165 mg/ L chloroquine (therapeutic range 20 to 200 mg/L) was obtained. Minocycline was given at a dosage of one 100 mg minocycline tablet twice daily for 45 days. This dosage had to be reduced to 100 mg daily from day 5 to day 8 because of vertigo. Vestibular toxicity manifesting as dizziness, ataxia and nausea is a common side effect of this tetracycline. The plasma concentration of minocycline, determined by HPLC, was 2.1 mg/L. The serum and respective plasma concentrations were determined 5 weeks after onset of treatment and 14 h after the last medication. The PCR for T. whipplei in the CSF was negative, both 12 and 24 months later. The patient has been asymptomatic now for more than 9 years after the initial examination and treatment. Obviously, this new treatment option, found to be efficacious in a single patient, should be evaluated in a prospective trial. The regimen is attractive as the combination of minocycline and chloroquine can be given orally. However, vestibular side effects (occurring in .70% of women taking 100 mg of minocycline every 12 h) will render any study difficult. Our male patient had to reduce the dose of minocycline for several days.

Whipple’s disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma whipplei, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-β1, having an increased frequency of the genotype TGF-β1+869C/C,+915C/C [12.3 % vs. 3.81 %, odds ratio (OR) = 4.131, p = 0.0002] and high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34 % vs. 1.17 %, OR = 5.09, p = 0.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.

Background: Whipple disease, which is caused by infection with Tropheryma whipplei, can be treated effectively with antimicrobials. Occasionally, inflammation reappears after initial improvement; this is often interpreted as refractory or recurrent disease. However, polymerase chain reaction for T. whipplei in tissue is sometimes negative during reinflammation, indicating absence of vital bacteria, and this reinflammation does not respond to antimicrobials but does respond to steroids. Objective: To demonstrate that the immune reconstitution inflammatory syndrome (IRIS) occurs in patients treated for Whipple disease. Design: Cohort study. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN45658456) Setting: 2 academic medical centers in Germany. Methods: 142 patients treated for Whipple disease out of a cohort of 187 were observed for reappearance of inflammatory signs after effective antibiotic therapy. Definitions of IRIS in HIV infection, tuberculosis, and leprosy were adapted for application to Whipple disease. Results: On the basis of study definitions, IRIS was diagnosed in 15 of 142 patients. Symptoms included fever, arthritis, pleurisy, erythema nodosum, inflammatory orbitopathy, small-bowel perforation, and a hypothalamic syndrome. Two patients died. There was a positive correlation with previous immunosuppressive treatment and a negative correlation with previous diarrhea and weight loss. Limitations: The study was observational and thus has inherent weaknesses, such as incomplete and potentially selective data recording. Conclusion: The immune reconstitution inflammatory syndrome was diagnosed in about 10% of patients with Whipple disease in the study cohort; the outcome varied from mild to fatal. Patients who had had previous immunosuppressive therapy were at particular risk. An immune reconstitution syndrome should be considered in patients with Whipple disease in whom inflammatory symptoms recur after effective treatment. Early diagnosis and treatment with steroids may be beneficial; prospective studies are needed. Primary Funding Source: European Commission and Deutsche Forschungsgemeinschaft.

BACKGROUND & AIMSWhipple's disease is a chronic infection caused by the actinomycete Tropheryma whipplei. We conducted a randomized controlled trial of the efficacy of antimicrobials that are able to cross the blood-brain barrier and to which T whipplei is susceptible.METHODSPatients from central Europe with previously untreated Whipple's disease (n = 40) were assigned randomly to groups given daily infusions of either ceftriaxone (1 x 2 g, 20 patients) or meropenem (3 x 1 g, 20 patients) for 14 days, followed by oral trimethoprim-sulfamethoxazole for 12 months. The primary outcome measured was maintenance of remission for 3 years, determined by a composite index of clinical and laboratory data as well as histology.RESULTSAll patients were observed for the entire follow-up period (median, 89 mo; range, 71-128 mo); all achieved clinical and laboratory remission. Remission was maintained in all patients during the time of observation, except for 2 who died from unrelated causes. A single patient with asymptomatic cerebrospinal infection who was resistant to both treatments responded to chloroquine and minocycline. The odds ratio for the end point (remission for at least 3 years) was 0.95 (95% confidence interval, 0.05-16.29; P = 1.0).CONCLUSIONSThis was a randomized controlled trial to show that treatment with ceftriaxone or meropenem, followed by trimethoprim-sulfamethoxazole, cures patients with Whipple's disease. One asymptomatic individual with infection of the cerebrospinal fluid required additional therapy.

BACKGROUND & AIMS:Whipple's disease is a systemic, chronic, relapsing disorder caused by a combination of environmental (Tropheryma whipplei) and unknown host factors. Because it is a rare disease, the association between HLA type and Whipple's disease has been studied in only small numbers of patients; these studies have led to conflicting results. We aimed to investigate whether disease phenotype and outcome are associated with HLA type in 122 patients with Whipple's disease.METHODS:Genomic DNA was collected from 103 German, 11 Italian, and 8 Austrian patients with Whipple's disease, along with 62 healthy Austrian workers exposed to T whipplei (14 stool samples contained the bacterium). HLA class I and II alleles were identified by polymerase chain reaction analysis. Patient genotypes were compared with those of healthy German and Austrian populations; data for Italian controls were obtained from the Pavia HLA bone marrow donors' bank.RESULTS:HLA-DRB1*13 and DQB1*06 alleles occurred significantly more frequently in patients with Whipple's disease but not in healthy individuals who had been exposed to T Whipplei. The cumulative odds ratios for disease were 2.23 for the DRB1*13 allele (P < .0001) and 2.25 for the DQB1*06 allele (P < .0001).CONCLUSIONS:DRB1*13 and DQB1*06 alleles were found to be risk factors in the largest HLA study ever performed in patients with Whipple's disease.

Tropheryma whipplei, the causative agent of Whipple's disease, is associated with various clinical manifestations as well as an asymptomatic carrier status, and it exhibits genetic heterogeneity. However, relationships that may exist between environmental and clinical strains are unknown. Herein, we developed an efficient genotyping system based on four highly variable genomic sequences (HVGSs) selected on the basis of genome comparison. We analysed 39 samples from 39 patients with Whipple's disease and 10 samples from 10 asymptomatic carriers. Twenty-six classic gastrointestinal Whipple's disease associated with additional manifestations, six relapses of classic Whipple's disease (three gastrointestinal and three neurological relapses), and seven isolated infections due to T. whipplei without digestive involvement (five endocarditis, one spondylodiscitis and one neurological infection) were included in the study. We identified 24 HVGS genotypes among 39 T. whipplei DNA samples from the patients and 10 T whipplei DNA samples from the asymptomatic carriers. No significant correlation between HVGS genotypes and clinical manifestations of Whipple's disease, or asymptomatic carriers, was found for the 49 samples tested. Our observations revealed a high genetic diversity of T. whipplei strains that is apparently independent of geographical distribution and unrelated to bacterial pathogenicity. Genotyping in Whipple's disease may, however, be useful in epidemiological studies.

Codon 104(−G), a heterozygous frameshift mutation in exon 2 of HBB, resulted in a dominantly inherited β0-phenotype with mild anemia in a German kindred, and thalassemia intermedia in the index patient. A co-inherited α gene triplication, long-term transfusion therapy, and ineffective erythropoiesis were confounding factors.

BACKGROUND AND OBJECTIVE:Abdominal pain is generally believed to be a symptom of intra-abdominal disease. When no pathological findings are evident, abdominal pain is considered functional. Abdominal pain, however, may also originate in the abdominal wall.METHODS:Consecutive patients with unexplained abdominal pain were enrolled in a prospective observational study in a gastroenterologic clinic during a period of three years. The following criteria were tested: Can abdominal pain be elicited by physical movement? Is the source of pain localized to a circumscribed site in the abdominal wall? Can pain be provoked by digital palpation in this area and does pain increase when the abdominal muscles are tensed?RESULTS:Clinical examination of 55 patients revealed small painful pits in the abdominal wall with varying intensity of pain when the abdominal muscles were contracted: in 39 patients the painful area was located in the semilunar line, in seven patients the pain originated in the linea alba between xiphoid and umbilicus, in five cases the painful spots were situated within the rectus muscle, and in four patients the pain was localized along the costal arch. Of the 39 patients with pain in the semilunar line, 16 had a BMI > 30, 12 presented with anxiety and depression, and 10 reported bloating and straining during defecation. Pain in the rectus muscle was associated with exercise. The patients with pain in the linea alba and at the costal arch suffered from obesity, anxiety or depression.CONCLUSIONS:These findings suggest that repeated forceful contractions of the abdominal wall muscles during exercise and straining, as well as chronic inflation of the abdominal wall by fat pads and by bloating, may cause strain and pain in the abdominal wall at sites predestined by anatomy. Symptom-specific anxiety may be a consequence of chronic unexplained abdominal pain. A novel classification of abdominal wall pain is proposed. The correct diagnosis will avoid repeated and costly investigations and relieve the patient's anxiety.