Mesenteric Lymphadenitis

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Background

Mesenteric lymphadenitis refers to inflammation of the mesenteric lymph nodes and is considered present if a cluster of three or more lymph nodes, each measuring 5 mm or greater, is detected in the right lower quadrant mesentery.[1] This process may be acute or chronic, depending on the causative agent, and it causes a clinical presentation that is often difficult to differentiate from acute appendicitis,[1, 2, 3]  particularly in children.[4, 5]

Pathophysiology

Microbial agents are thought to gain access to the lymph nodes via the intestinal lymphatics. Organisms subsequently multiply and, depending on the virulence of the invading pathogen, elicit varying degrees of inflammation and, occasionally, suppuration.[6]

Grossly, the lymph nodes are enlarged and often soft. The adjourning mesentery may be edematous, with or without exudates. If a contiguous primary source of infection (eg, the appendix) is present, evidence of inflammation is often apparent.

Microscopically, the lymph nodes show nonspecific hyperplasia and, in suppurative infection, necrosis with numerous pus cells.

Etiology

Numerous organisms have been cultured from mesenteric lymph nodes and blood, such as beta-hemolytic streptococcus, Staphylococcus species, Escherichia coli, Streptococcus viridans, Yersinia species (responsible for most cases currently), Mycobacterium tuberculosis, Giardia lamblia, and non– Salmonella typhoid. Viruses, such as coxsackieviruses (A and B), rubeola virus, and adenovirus serotypes 1, 2, 3, 5, and 7, have also been implicated.

Mesenteric node involvement can also be part of infectious Epstein-Barr virus (EBV), acute human immunodeficiency virus (HIV) infection, and catscratch disease (CSD).

The frequent association of this condition, especially in children with upper respiratory tract infection, has popularized a theory that swallowed pathogen-laden sputum may be the primary source of infection.

Fecal-oral transmission occurs in Y enterocolitica infection and may present as a common source outbreak. This infection has also been associated with meat, milk, and water contamination. Rarely, person-to-person or zoonotic contacts with fecal carriers can lead to infection.

Epidemiology

United States data

The true incidence of this disease is not known, because it can be easily missed or mistaken for other diagnoses. The condition is generally thought to be common. Up to 20% of patients undergoing appendectomy have been found to have nonspecific mesenteric adenitis.

International data

Frequency is similar to that of the United States. Yersinia enterocolitica infection has a geographic variation. This infection is most common in the temperate countries of Europe, North America, and Australia; it has been particularly noted in Eastern Europe.

Sex- and age-related demographics

The condition affects males and females equally. Yersinia infection is more common in boys than in girls.

Mesenteric lymphadenitis can occur in adults but is more common in children and adolescents younger than 15 years, and this condition during childhood or adolescence is linked to a significantly reduced risk of ulcerative colitis in adulthood.[7]

Frisch et al reviewed Swedish and Danish cohort studies involving 709,353 patients who had undergone appendicectomy and were followed up for subsequent ulcerative colitis to determine the role of appendicitis and mesenteric lymphadenitis in the risk of ulcerative colitis following appendicectomy.[7] The investigators also studied the impact of appendicectomy in 224,483 patients with a family history (parents or siblings) of inflammatory bowel disease and found that regardless of familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence is linked to a significantly reduced risk of ulcerative colitis in adulthood.[7]

Prognosis

The prognosis is good. Typically, complete recovery can be expected without specific treatment. Death is rare.

Morbidity/mortality

Mesenteric lymphadenitis generally is a benign disease, but patients with sepsis may have a fatal outcome.

Complications

Complications of mesenteric lymphadenitis include the following:

Patient Education

Explain the benign nature of the disease to patients; however, because there is a risk of recurrence, also explain that they must seek prompt medical attention in each instance to exclude other more emergent etiologies.

In cases of Yersinia infection as the underlying infectious agent, instruct patients to avoid unpasteurized milk, raw pork (particularly chitterlings), and contaminated water.[6]

History

The disease may have a variable course, depending on the patient's age and condition and/or the pathogenic properties of the causative organisms.[6]  The onset and progression of mesenteric lymphadenitis may be insidious or, sometimes, dramatic. 

Clinical features of associated organ involvement, such as enterocolitis or ileitis in Yersinia infection, may be present. Clinical presentations include the following:

Physical Examination

Although no set of physical findings is pathognomonic of mesenteric lymphadenitis, the following may be found in affected patients:

Classification

Mesenteric adenitis can be divided into two distinct groups: primary and secondary.[1]

On imaging, primary mesenteric adenitis is described as right-sided mesenteric lymphadenopathy that does not have an identifiable acute inflammatory process or demonstrates only mild (<5 mm) wall thickening of the terminal ileum.[1] The etiology may be an underlying infectious terminal ileitis.

Secondary mesenteric adenitis on imaging studies demonstrates lymphadenopathy that is associated with a specific, identifiable intraabdominal inflammatory process.[1] In the presence of clearly detectable terminal ileal thickening (eg, Crohn disease, infectious ileitis), the mesenteric adenitis is considered secondary.

Laboratory Studies

The following laboratory studies may aid in the evaluation of patients with suspected mesenteric lymphadenitis:

Specific cytokine levels in conjunction with WBC counts may help to differentiate between pediatric acute mesenteric lymphadenitis and acute appendicitis. In a prospective study (2010-2013) of 31 children with acute appendicitis, 26 with acute mesenteric lymphadenitis, and 17 with elective noninflammatory surgical disease (control group), Zviedre et al found that a 1-hour preoperative interleukin (IL)-6 cut-off value of 4.3 pg/mL (67.7% sensitivity; 76.9% specificity) combined with a WBC count cut-off value of 10.7 × 103/μL (71.0% sensitivity; 46.2% specificity) was more sensitive for acute appendicitis.[8]

Other laboratory studies

In patients subjected to laparotomy, lymph node specimens may show evidence of inflammation or suppuration, and culture may yield a causative organism.

In the presence of mesenteric lymphadenitis with obvious terminal ileal thickening (eg, Crohn disease, infectious ileitis) (ie, secondary mesenteric lymphadenitis), obtain/perform endoscopic biopsies, stool cultures, or small-bowel barium studies to determine the underlying cause of the adenitis, particularly in cases refractory to conservative therapy.[1]

Imaging Studies

Computed tomography scanning

Contrast computed tomography (CT) scanning demonstrates enlarged mesenteric lymph nodes, with or without associated ileal or ileocecal wall thickening, and a normal appearing appendix. In mesenteric adenitis, lymph nodes tend to be larger, greater in number, and more widely distributed than in appendicitis. Rao et al specified the criterion of 3 or more nodes with a short-axis diameter of at least 5 clustered in the right lower quadrant. CT scanning is also important to exclude other differential diagnoses, especially acute appendicitis. 

Magnetic resonance imaging

Contrast-enhanced magnetic resonance imaging (MRI) can differentiate between acute appendicitis and other causes of pediatric abdominal pain, with good visualization of the appendix.[9]  More information is needed whether contrast enhancement with MRI has an advantage over non-enhanced MRI in this setting.

Ultrasonography

Abdominal ultrasonographic scanning with Doppler scanning is a useful adjunct for excluding other differential diagnoses.[2, 4, 10] For instance, ultrasonographic demonstration of mural thickening of the terminal ileum plus mesenteric thickening is indicative of regional enteritis. Focal abdominal tenderness in response to transducer pressure is common. Ultrasonography is often the preferred initial diagnostic procedure, especially in children with uncomplicated abdominal pain.

A study by Ja Lim et al supported the use of ultrasonography in the diagnosis of mesenteric lymphadenitis. The retrospective study involved 100 children with clinically suspected intussusception, with abdominal ultrasonography instead demonstrating the presence of mesenteric lymphadenitis in 13 of these patients. Other conditions identified in the study included ileocolitis, terminal ileitis, choledochal cyst, accessory spleen torsion, small bowel ileus, midgut volvulus with bowel ischemia, and hydronephrosis, as well as intussusception (in 37 patients).[11]

Sheridan et al demonstrated the potential utility of ultrasonography to stratify patients with acute appendix into different treatment strategies.[12] They found that (1) a fluid-filled appendix always correlated with a suppurative or mixed pathologic appearance that likely warranted operative intervention, and (2) a lymphoid-predominant pathologic appearance occurred only in cases where appendiceal wall thickening alone was seen on ultrasonography.[12]

Medical Care

The objective of medical management is to quickly identify patients who require surgical intervention (ie, for appendicitis) and to refer appropriately. Inpatient care is indicated for patients with complications. When the diagnosis is not clear, admission for observation may be necessary.

Empiric, broad-spectrum antibiotics may be used in moderately to severely ill patients and should cover Yersinia strains, commonly causative in mesenteric adenitis. General supportive care includes hydration and pain medication after excluding acute surgical abdomen. Patients with mild, uncomplicated presentations do not require antibiotics, and supportive care generally suffices.

Make early contact with a general surgeon while evaluating the patient to exclude etiologies that require urgent surgery.

Prehospital care

Prompt transfer of patients to a facility where an appropriate workup can be conducted is the most important prehospital goal.

Vascular access and saline infusion are beneficial for patients who are more ill and have volume depletion.

Emergency department treatment

Carefully evaluate patients to exclude potentially life-threatening alternative diagnoses.

Initiate appropriate workup. Consult with a general surgeon when indicated.

Hospital admission

Patients with volume depletion, significant electrolyte imbalance, and/or sepsis require hospital admission.

In instances for which diagnosis is not clear, inpatient observation and further workup may be appropriate.

No particular diet is recommended, although temporary withholding of oral intake may be necessary while nausea and vomiting resolve and initially until a definitive diagnosis is confirmed.

Discharge

Schedule early outpatient follow-up visits to ensure complete resolution of symptoms.

No further diagnostic tests are required for patients who recover completely. This is the case for most patients.

Surgical Care

Surgery is usually indicated in suppuration and/or abscess, with signs of peritonitis, or if acute appendicitis cannot be excluded with certainty.

At laparotomy, the diagnosis is generally clear. An appendectomy should be performed in view of the tendency for recurrence of lymphadenitis and the difficulty in differentiating adenitis from appendicitis.

Medication Summary

Antibiotics are often started empirically in moderately to severely ill patients, using broad-spectrum antibiotics intended to cover the commonly associated pathogens. Antibiotic treatment should then be adjusted based on the sensitivity of the isolated pathogen. Treatment duration is variable based on the cause and severity of illness. For uncomplicated cases, antibiotic treatment is not necessary.

Metronidazole (Flagyl, Protostat)

Clinical Context:  Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Exerts a bactericidal effect by inhibiting protein synthesis. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).

Clindamycin (Cleocin)

Clinical Context:  Lincosamide used for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, thus causing cessation of RNA-dependent protein synthesis.

Ampicillin (Omnipen, Polycillin)

Clinical Context:  Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Amoxicillin (Amoxil, Trimox)

Clinical Context:  Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Ciprofloxacin (Cipro)

Clinical Context:  Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Trovafloxacin (Trovan) overcomes many of these limitations. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.

Imipenem/cilastin (Primaxin)

Clinical Context:  For treatment of multiple organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity.

Cefoxitin (Mefoxin)

Clinical Context:  Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

Ticarcillin/clavulanate (Timentin)

Clinical Context:  Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive bacteria, most gram-negative bacteria, and most anaerobes.

Ampicillin/sulbactam (Unasyn)

Clinical Context:  Drug combination of beta-lactamase inhibitor with ampicillin. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.

Class Summary

When indicated, empiric antimicrobial therapy must be comprehensive and should cover the likely pathogens in the context of the clinical setting. Given the predominance of Y enterocolitica, initial antibiotic selection from trimethoprim-sulfamethoxazole (TMP-SMX), third-generation cephalosporins, fluoroquinolones, aminoglycosides, and doxycycline should be considered. These agents provide broad coverage for enteric pathogens.

Author

Alan S Putrus, MBChB, Fellow, Department of Gastroenterology, St John Providence/Providence Park Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Michael H Piper, MD, Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates, PLC

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine

Disclosure: Received grant/research funds from Novartis for other; Received grant/research funds from Bayer for other; Received grant/research funds from Otsuka for none; Received grant/research funds from Bristol Myers Squibb for other; Received none from Scynexis for none; Received grant/research funds from Salix for other; Received grant/research funds from MannKind for other.

Chief Editor

Burt Cagir, MD, FACS, Clinical Professor of Surgery, The Commonwealth Medical College; Director, General Surgery Residency Program, Robert Packer Hospital; Attending Surgeon, Robert Packer Hospital and Corning Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Mukul Arya, MD, Associate Professor of Internal Medicine, Weill Cornell Medical College; Assistant Director of Therapeutic Endoscopy, Department of Gastroenterology and Internal Medicine, Wyckoff Heights Medical Center

Disclosure: Nothing to disclose.

Norvin Perez, MD, Medical Director, Juneau Urgent and Family Care

Disclosure: Nothing to disclose.

Oluyinka S Adediji, MD, MBBS, Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama

Disclosure: Nothing to disclose.

Vivek V Gumaste, MD, Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center at Elmhurst; Program Director of GI Fellowship (Independent Program); Regional Director of Gastroenterology, Queens Health Network

Disclosure: Nothing to disclose.

References

  1. Macari M, Hines J, Balthazar E, Megibow A. Mesenteric adenitis: CT diagnosis of primary versus secondary causes, incidence, and clinical significance in pediatric and adult patients. AJR Am J Roentgenol. 2002 Apr. 178 (4):853-8. [View Abstract]
  2. Toorenvliet B, Vellekoop A, Bakker R, et al. Clinical differentiation between acute appendicitis and acute mesenteric lymphadenitis in children. Eur J Pediatr Surg. 2011 Mar. 21 (2):120-3. [View Abstract]
  3. Moore MM, Kulaylat AN, Brian JM, et al. Alternative diagnoses at paediatric appendicitis MRI. Clin Radiol. 2015 Aug. 70 (8):881-9. [View Abstract]
  4. Sanchez TR, Corwin MT, Davoodian A, Stein-Wexler R. Sonography of abdominal pain in children: appendicitis and its common mimics. J Ultrasound Med. 2016 Mar. 35 (3):627-35. [View Abstract]
  5. Gross I, Siedner-Weintraub Y, Stibbe S, et al. Characteristics of mesenteric lymphadenitis in comparison with those of acute appendicitis in children. Eur J Pediatr. 2016 Dec 16. [View Abstract]
  6. Zinczuk J, Wojskowicz P, Kisluk J, Fil D, Kemona A, Dadan J. Mesenteric lymphadenitis caused by Yersinia enterocolitica. Prz Gastroenterol. 2015. 10 (2):118-21. [View Abstract]
  7. Frisch M, Pedersen BV, Andersson RE. Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark. BMJ. 2009 Mar 9. 338:b716. [View Abstract]
  8. Zviedre A, Engelis A, Tretjakovs P, Jurka A, Zile I, Petersons A. Role of serum cytokines in acute appendicitis and acute mesenteric lymphadenitis among children. Medicina (Kaunas). 2016. 52 (5):291-7. [View Abstract]
  9. Koning JL, Naheedy JH, Kruk PG. Diagnostic performance of contrast-enhanced MR for acute appendicitis and alternative causes of abdominal pain in children. Pediatr Radiol. 2014 Aug. 44 (8):948-55. [View Abstract]
  10. Ackerman SJ, Irshad A, Anis M. Ultrasound for pelvic pain II: nongynecologic causes. Obstet Gynecol Clin North Am. 2011 Mar. 38 (1):69-83, viii. [View Abstract]
  11. Ja Lim K, Lee K, Yoon DY, et al. The role of US in finding intussusception and alternative diagnosis: a report of 100 pediatric cases. Acta Radiol. 2015 Feb. 56 (2):228-33. [View Abstract]
  12. Sheridan AD, Ehrlich L, Morotti RA, Goodman TR. Sonographic distinction between acute suppurative appendicitis and viral appendiceal lymphoid hyperplasia ("pink appendix") with pathological correlation. Ultrasound Q. 2015 Jun. 31 (2):95-8. [View Abstract]

Primary mesenteric lymphadenitis in 27-year-old woman with right lower quadrant pain (RLQ). This axial computed tomography scan was obtained with intravenous and oral contrast material at the level of the upper pelvis and shows a cluster of lymph nodes (<em>arrows</em>) in the RLQ mesentery. The appendix and terminal ileum (not shown) were normal. The patient was discharged from the emergency department and improved without therapy.

Secondary mesenteric lymphadenitis in 14-year-old girl with right lower quadrant (RLQ) pain and appendicitis. Image A, left: This axial computed tomography (CT) scan was obtained with intravenous and oral contrast material at the level of the upper pelvis. A cluster of lymph nodes (<em>arrows</em>) can be seen in the RLQ mesentery. <em>Image B, right:</em> This axial CT scan was obtained at the level of the appendix. It shows a dilated, fluid-filled appendix (<em>arrow</em>) with an enhanced wall. Surgery confirmed the diagnosis of appendicitis.