Die führende Diagnose - Eine 23jährige Frau stellt sich mit seit einer Stunde andauernden, kolikartigen Bauchschmerzen in der Ambulanz vor...

A 23-year-old black woman presented to the emergency department with diffuse, colicky abdominal pain of 1 hour's duration. The pain was followed by nausea and episodes of bilious vomiting and did not radiate or change with the patient's position. She did not report fever, chills, diarrhea, hematochezia, or melena.
The differential diagnosis of acute abdominal pain in young adults is broad and includes appendicitis, peptic ulcer disease, nephrolithiasis, infectious enteritis, inflammatory bowel disease, hepatobiliary diseases such as cholecystitis, pancreatitis, and referred pain from pneumonia. In young women, gynecologic conditions (such as ectopic pregnancy, endometriosis, and pelvic inflammatory disease) are additional important considerations.
Nausea and bilious vomiting are consistent with hepatobiliary disease, pancreatitis, and small-bowel disorders such as obstruction, infection, and Crohn's disease. The diffuse nature of the pain in this patient makes hepatobiliary disease unlikely. The absence of reported diarrhea or gastrointestinal bleeding would argue against endoluminal infection or inflammatory bowel disease.
Diffuse abdominal pain may also suggest bowel obstruction or ischemia, or metabolic disease such as diabetic ketoacidosis or acute intermittent porphyria, although the latter condition is rare. I would first want to rule out evidence of peritonitis, which in a young woman may result from conditions such as ectopic pregnancy, a ruptured tubo-ovarian abscess or appendix, or a perforated ulcer.
The patient reported that a similar episode had occurred 6 months previously. It lasted 30 minutes and resolved on its own. At that time, she passed red blood from the rectum once but did not seek medical attention. Her other medical history included an elective abortion at 20 years of age and anemia and metromenorrhagia, neither of which had been further evaluated. She had no history of abdominal surgeries. She said that she did not use tobacco, alcohol, or illicit drugs, and she worked as a legal assistant. She was unaware of any gastrointestinal or sickle cell disease in her family.
A history of bright red blood from the rectum, if confirmed, would indicate endoluminal disease of the gastrointestinal tract — presumably the lower tract; if the source was the upper gastrointestinal tract, red blood would indicate very rapid transit, yet the previous episode was self-limited, without hemodynamic compromise. Bilious vomiting suggests a site proximal to the ileocecal valve. Inflammatory bowel disease is a leading possibility. The combination of vomiting and the absence of changes in stool volume, color, and frequency could be explained by a stricture complicating Crohn's disease, and it could also explain the patient's anemia, although her history of metromenorrhagia provides an alternative explanation for that condition. An underlying hematologic disorder (such as sickle cell disease, thalassemia, or glycerophosphoryl diester phosphodiesterase deficiency, all of which are more common in blacks) might also underlie her previously diagnosed anemia. Other less common causes of small-intestinal bleeding and pain include tumors, mesenteric ischemia, Meckel's diverticulum (although the pain is typically less severe), and endometrial deposits along the intestinal tract with pain that may correlate with the periodicity of the menses.
On examination, the patient was afebrile, with a heart rate of 100 beats per minute, a respiratory rate of 16 breaths per minute, an oxygen saturation of 100% while she was breathing ambient air, and a blood pressure of 115/65 mm Hg. Her height was 65 in. (165.1 cm), and she weighed 115 lb (52.3 kg). She was restless on the gurney, clutching her abdomen. Her sclerae were anicteric, and her conjunctivae were pale. The oropharynx was normal, and the neck was supple, without lymphadenopathy. The heart sounds were regular, and the lungs clear. There was no chest-wall or flank tenderness. Abdominal examination revealed hyperactive bowel sounds and diffuse tenderness on palpation without rebound tenderness, organomegaly, or masses. The rectal examination showed no masses. A stool sample was brown and was negative for occult blood. The pelvic examination revealed no masses, cervical motion, or adnexal tenderness. There was no edema in the legs. The neurologic examination was normal.

The observations that the patient is restless (as compared with the still appearance that would be expected in diffuse peritonitis), that she is clutching her abdomen but not avoiding touch, and that she has hyperactive bowel sounds and no rebound tenderness argue against generalized peritonitis, although these findings do not rule out early peritoneal inflammation. On this occasion, there is no occult blood in her stool, but conjunctival pallor suggests profound anemia. Given her history, I continue to be concerned about gastrointestinal blood loss, and I wonder in particular about inflammatory bowel disease as the cause of her condition.
Admission to the hospital is warranted to determine the cause of her severe pain. A negative serum human chorionic gonadotropin (hCG) test would rule out ectopic pregnancy. If routine laboratory tests do not point to the source of pain, urgent abdominal imaging with computed tomography (CT) is indicated. CT is more sensitive than plain radiography for detecting the presence and source of intraabdominal free air, and it may reveal small-bowel obstruction or bowel-wall thickening. This latter result, although nonspecific, would be compatible with bowel-wall edema due to ischemia, infection, inflammation, or neoplastic infiltration. Given my low suspicion for infection, this finding might lead to endoscopic evaluation of the bowel.

The serum sodium, potassium, and calcium levels were normal. The blood urea nitrogen level was 9 mg per deciliter (3.2 mmol per liter), creatinine 0.6 mg per deciliter (53 µmol per liter), lipase 22 U per liter (normal range, 1 to 60), aspartate aminotransferase 25 U per liter (normal range, 8 to 31), alanine aminotransferase 10 U per liter (normal range, 7 to 31), alkaline phosphatase 55 U per liter (normal range, 39 to 117), and total bilirubin 0.3 mg per deciliter (5.1 µmol per liter) (normal range, 0.1 to 1.2 mg per deciliter [2 to 21 µmol per liter]). The white-cell count was 6400 per cubic millimeter, with 87% neutrophils, 9% lymphocytes, and 4% monocytes. The hematocrit was 23%, with a mean corpuscular volume of 65 µm3. A peripheral-blood smear showed 2+ microcytosis, 2+ hypochromia, and no other abnormal cells. A serum test for hCG was negative. Dipstick testing of a specimen of voided urine revealed a specific gravity of 1.022 and a pH of 5.0; tests for protein, leukocyte esterase, nitrites, and blood were negative. Urine microscopical examination showed no white or red cells.

These results rule out ectopic pregnancy. Pyelonephritis would be unlikely without pyuria, and, although no amylase level was reported, the normal lipase level argues against pancreatitis. Advanced cholecystitis and cholangitis are unlikely given the normal results of the liver-function tests. A normal white-cell count soon after the onset of symptoms does not rule out bowel obstruction or inflammatory processes such as appendicitis. The most salient findings are the low hematocrit and mean corpuscular volume. Iron deficiency and thalassemia are the most common causes of these values. In this patient with metromenorrhagia and bleeding from the rectum, iron deficiency is a more likely cause. Although her menorrhagia could account for her iron deficiency, I am very suspicious about a bleeding lesion in the bowel. Her severe pain makes me particularly worried about obstruction or perforation. I would order a CT scan of the abdomen before considering endoscopic evaluation.
A CT scan of the abdomen showed intussusception of a segment of small intestine (Figure 1).
Figure 1. CT Scan of the Abdomen.
Small-bowel intussusception is shown by the "bowel-within-bowel" appearance (arrow) created when the leading edge telescopes into the lumen.

Small-bowel intussusception in a 23-year-old is unusual. This finding suggests that there is a "leading edge" (protruding tissue) that has caused the small intestine to telescope on itself. During normal intestinal propulsion, such tissue becomes an intraluminal bolus and moves distally, causing ischemia as the blood supply is compromised. Causes of small-intestinal intussusception include tumors, endometrial implants, foreign bodies, and unusual endoluminal infections such as ascariasis. In the United States, benign and malignant neoplasms are the most likely causes of small-bowel intussusception. I would obtain surgical consultation.

The patient received a transfusion of 2 units of packed red cells before laparoscopically assisted surgical exploration. Intraoperatively, a jejunojejunal intussusception was identified, and a firm irregular mass was palpated at the leading edge of the intussusception. There was no evidence of ischemia. The intussusception was manually reduced and the mass and adjacent jejunum were then resected. A pedunculated polyp measuring 4 by 2 by 2 cm was sent to the pathology laboratory.

The differential diagnosis of small-bowel polyps includes adenomas, adenocarcinomas, lymphomas, carcinoid tumors, metastases, hamartomas, and hyperplastic polyps. Primary or metastatic intestinal cancer would be unusual at this age. Of the benign tumors, hamartomas can protrude into the intestinal lumen and cause intussusception. Hamartomatous polyps are characteristic of the Peutz–Jeghers syndrome, a disorder that also includes pigmented mucocutaneous lentigines. While awaiting the interpretation of the pathological examination, I would examine the patient for these occasionally overlooked findings.
On closer inspection, several small hyperpigmented lentigines were detected on the patient's fingers (Figure 2A), tongue, and everted lips (Figure 2B). She stated that these lentigines had been present since childhood.
Figure 2. Hyperpigmented Lesions.
Hyperpigmented lesions are shown on the fingers (Panel A) and on the lips (Panel B).

The Peutz–Jeghers syndrome is my leading diagnosis. It would explain the mucocutaneous lentigines and intestinal polyp with bleeding. I would also expect at least one of the patient's relatives to have the disease. The specimen must be evaluated for evidence of a malignant condition that may occur in patients with the Peutz–Jeghers syndrome.
Histologic analysis (Figure 3) showed that the polyp was a hamartoma, consistent with the Peutz–Jeghers syndrome. There was no evidence of a malignant condition. When the patient's mother arrived after the operation, she said that her sister had been diagnosed with the syndrome. The patient was discharged on the fourth hospital day.

Commentary
In 1921, Peutz reported the combination of mucocutaneous melanin spots and gastrointestinal polyposis in a Dutch family.1 Jeghers described 10 additional cases in 1949, reinforcing Peutz's findings of a unique familial syndrome.2 The Peutz–Jeghers syndrome is an autosomal dominant disorder caused by a germ-line mutation of the STK11 gene, and it affects men and women equally and with high penetrance. Pigmented mucocutaneous lesions that are present in nearly all patients by 2 years of age occur most commonly on the lips and perioral region (in 94% of patients) followed by the hands (in 74%), buccal mucosa (in 66%), and feet (in 62%).3 Although they are similar in size to freckles (1 to 5 mm), lesions associated with the Peutz–Jeghers syndrome are distinguished by their perioral predilection, appearance at an early age, and growth in size and number until puberty, after which the skin lesions begin to regress, although they do not do so completely.3
A hallmark of the Peutz–Jeghers syndrome is the presence of hamartomatous polyps of the gastrointestinal tract, which is seen in 88% of patients. Hamartomatous polyps typically range in size from 0.1 to 5.0 cm and occur most commonly in the small intestine (in 64% of patients), colon (in 64%), stomach (in 49%), and rectum (in 32%).3,4 Rare reports describe polyps in the renal pelvis, urinary bladder, lungs, and nares.4 Hamartomatous polyps in the Peutz–Jeghers syndrome typically occur in patients between 10 and 30 years of age with symptoms of obstruction (in 43% of patients), abdominal pain (in 23%), bloody stool (in 14%), or anal extrusion of a polyp (in 7%).4 The most frequent complication of polyps is intussusception, which is reported in 47% of patients. The location of intussusception is the small bowel in 95% of patients with this syndrome.3 Other sequelae include obstruction due to lumen occlusion by the polyp, intestinal infarction, and autoamputation of the polyp.3
Patients with the Peutz–Jeghers syndrome are also at high risk for intestinal and extraintestinal cancer.5 The increase in the incidence of cancer begins around 30 years of age, and the cumulative lifetime risk is at least 85%.4,6 The most common cancers are gastrointestinal (in 57% of patients) and breast (in 45%).6 The incidences of tumors of the ovary, cervix, pancreas, lung, uterus, and testes are also increased.4 Germ-line mutations in STK11, a suspected tumor-suppressor gene located on chromosome 19p13.3, have been identified in 70% of families with the Peutz–Jeghers syndrome.7,8
To our knowledge, no prospective studies of cancer screening have been conducted in patients with the Peutz–Jeghers syndrome. On the basis of the markedly elevated lifetime cancer risk, experts have adopted the National Comprehensive Cancer Network recommendations for colorectal and breast-cancer screening for patients at high risk for these malignant conditions. Experts also recommend heightened surveillance for cancers of the small bowel, pancreas, ovaries, uterus, and cervix.4
In retrospect, the patient's mucocutaneous lesions were quite typical of the Peutz–Jeghers syndrome. Had they been identified earlier, the diagnosis might have been suspected sooner. As a diagnostic tool, physical examination is notoriously imperfect.9,10 Signs of disease may wax or wane over time, the examiner's technique may be flawed, the examiner may be inattentive or inexperienced in interpreting the finding, or the examiner may be biased, expecting to find normal or abnormal results based on other facts of the case.11 The last two limitations may have played roles in this case. Anticipating a normal skin examination, examiners may have overlooked the lentigines or may have underappreciated the labial involvement as a key feature distinguishing the Peutz–Jeghers lentigines from ordinary freckles.
Only 5% of intussusceptions occur in adults. An underlying cause of intussusceptions is identified in 90% of adults with this condition, and benign and malignant neoplasms account for the majority of cases.12,13 Knowing that a neoplasm will be identified as the leading edge in most instances, the discussant recommended surgical evaluation for diagnosis and treatment. Surgery is routinely recommended for small-intestinal intussusceptions because of the high prevalence of malignant conditions and the recognized risk of recurrence.12,13,14 The combination of pigmented mucocutaneous lentigines and a hamartoma at the leading edge of an intussusception prompted a leading diagnosis of the Peutz–Jeghers syndrome.

References

1. Peutz JL. Over een zeer merkwaardige, gecombineerde familiaire polyposis van de slijmvliezen van den tractus intestinalis met die van de neuskeelholte en gepaard met eigenaardige pigmentaties van huid-en slijmvliezen. Ned Maandschr v Gen 1921;10:134-46.
2. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips, and digits: a syndrome of diagnostic significance. N Engl J Med 1949;241:993-1005, 1031.
3. Utsunomiya J, Gocho H, Miyanaga T, et al. Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J 1975;136:71-82.
4. Giardiello FM, Trimabath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006;4:408-415.
5. Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316:1511-1514.

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7. Hemminki A, Markie D, Tomlinson I, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998;391:184-187.
8. Lim W, Hearle N, Shah B, et al. Further observations on LBK1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 2003;89:308-313.
9. Wipf JE, Lipsky BA, Hirschmann JV, et al. Diagnosing pneumonia by physical examination: relevant or relic? Arch Intern Med 1999;159:1082-1087. [Free Full Text]
10. Oudega R, Moons KG, Hoes AW. Limited value of patient history and physical examination in diagnosing deep vein thrombosis in primary care. Fam Pract 2005;22:86-91. [Free Full Text] 11. McGee S. Reliability of physical findings. In: McGee S, ed. Evidence-based physical diagnosis. Philadelphia: W.B. Saunders, 2001:33-50.
12. Weilbaecher D, Bolin JA, Hearn D, Ogden W. Intussusception in adults: review of 160 cases. Am J Surg 1971;121:531-535.
13. Nagorney DM, Sarr MG, McIlrath DC. Surgical management of intussusception in the adult. Ann Surg 1981;193:230-236.
14. Erkan N, Haciyanli M, Yildirim M, Sayhan H, Vardar E, Polat AF. Intussusception in adults: an unusual and challenging condition for surgeons. Int J Colorectal Dis 2005;20:452-456.

NEJM Volume 357:2389-2393 December 6,2007 Number 23

Thomas E. Baudendistel, Amy K. Haase, and Faith Fitzgerald