Increasing circumstantial evidence suggests that not all patients with appendicitis will progress to perforation and that appendicitis that resolves may be a common event. Based on this theory and on indications of aberrant regulation of inflammation in gangrenous appendicitis, we hypothesized that phlegmonous and gangrenous appendicitis are different entities with divergent immunoregulation.
Blood samples were collected from patients with gangrenous appendicitis (n = 16), phlegmonous appendicitis (n = 21), and nonspecific abdominal pain (n = 42). Using multiplex bead arrays, we analyzed a range of inflammatory markers, such as interleukin (IL)-1ra, IL-1rβ, IL-2, IL-6, IL-10, IL-12p70, IL-15, and IL-17; interferon-γ; tumor necrosis factor; CXCL8; CCL2; CCL3; and matrix metalloproteinase (MMP)-1 MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13 in blood.
Compared with patients with phlegmonous appendicitis and nonspecific abdominal pain, the patients with gangrenous appendicitis had increased levels of the proinflammatory markers IL-6, CCL2, IL-17, MMP-8, and MMP-9 (P ≤ .04 each) accompanied by increased levels of the anti-inflammatory cytokines IL-1ra and IL-10 (P ≤ .02). Patients with phlegmonous appendicitis had increased levels of IL-10 only.
The finding of a pattern of inflammatory markers compatible with the highly inflammatory Th17 subset in sera from patients with gangrenous appendicitis, but not in phlegmonous appendicitis, supports the hypothesis that gangrenous and phlegmonous appendicitis are different entities with divergent immune regulation. Additional studies of the differential immunopathogenesis of phlegmonous and gangrenous appendicitis are warranted, as this may have important implications in the diagnosis and management of patients with suspicion of appendicitis.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The natural history and traditional management of appendicitis revisited: spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than an early diagnosis.World J Surg. 2007; 31: 86-92
- Surgery for appendicitis: is it necessary?.Surg Infect. 2008; 9: 481-488
- Randomized clinical trial of early laparoscopy in the management of acute non-specific abdominal pain.Brit J Surg. 1999; 86: 1383-1386
- Too few appendicectomies?.Lancet. 1964; 1: 1240-1242
- Indications for operation in suspected appendicitis and incidence of perforation.BMJ. 1994; 308: 107-110
- Acute nonspecific abdominal pain: a randomized, controlled trial comparing early laparoscopy versus clinical observation.Ann Surg. 2006; 244: 881-886
- Disconnect between incidence of nonperforated and perforated appendicitis: implications for pathophysiology and management.Ann Surg. 2007; 245: 886-892
- Resolving appendicitis is common: further evidence.Ann Surg. 2008; 247: 553
- Ultrasound documentation of spontaneously resolving appendicitis.Am J Emerg Med. 1993; 11: 51-53
- Spontaneously resolving acute appendicitis: clinical and sonographic documentation.Radiology. 1997; 205: 55-58
- Spontaneously resolving appendicitis: frequency and natural history in 60 patients.Radiology. 2000; 215: 349-352
- Resolving appendicitis: role of CT.Abdom Imaging. 2003; 28: 276-279
- Histological features of resolving acute, non-complicated phlegmonous appendicitis.Pathol Res Pract. 2000; 196: 89-93
- Incidence and case fatality rates for acute appendicitis in California. A population-based study of the effects of age.Am J Epidemiol. 1989; 129: 905-918
- Obstruction of the appendix lumen in relation to pathogenesis of acute appendicitis.Acta Chir Scand. 1983; 149: 789-791
- Appendectomy and protection against ulcerative colitis.N Engl J Med. 2001; 344: 808-814
- Appendectomy is followed by increased risk of Crohn's disease.Gastroenterology. 2003; 124: 40-46
- Incidence of appendicitis during pregnancy.Int J Epidemiol. 2001; 30: 1281-1285
- Innate immunity genes influence the severity of acute appendicitis.Ann Surg. 2004; 240: 269-277
- Different cytokine profiles in patients with a history of gangrenous or phlegmonous appendicitis.Clin Exp Immunol. 2006; 143: 117-124
- T(H)-17 cells in the circle of immunity and autoimmunity.Nat Immunol. 2007; 8: 345-350
- Interleukin-17 family members and inflammation.Immunity. 2004; 21: 467-476
- Regional and systemic cytokine responses to acute inflammation of the vermiform appendix.Ann Surg. 2003; 237: 408-416
- Human cytokine levels in nonperforated versus perforated appendicitis: molecular serum markers for extent of disease.Am Surg. 2002; 68: 1033-1036
- Novel serum inflammatory markers in acute appendicitis.Scand J Clin Lab Invest. 2002; 62: 579-584
Published online: November 06, 2009
Accepted: September 29, 2009
Supported by grants from the Health Research Council in Southeast Sweden (FORSS).
The work was supported by grants from the Health Research Council in Southeast Sweden (FORSS).
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.