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Annals of African Medicine
Annals of African Medicine Society
ISSN: 1596-3519
Vol. 9, Num. 4, 2010, pp. 200-202

Annals of African Medicine, Vol. 9, No. 4, October-December, 2010, pp. 200-202

Commentary

Appendicitis as an immunological disease: Why it is uncommon in Africans

Robert B Sanda

Department of Surgery, Drumheller Hospital, Alberta, Canada

Correspondence Address: Robert B Sanda, Department of Surgery, Drumheller Hospital, Alberta, Canada, robertsanda@yahoo.com

Code Number: am10047

PMID: 20935417

DOI: 10.4103/1596-3519.70953

Appendicitis is, doubtless, the quintessential surgical disease. It is the most ubiquitous emergent surgical disease. It is etiologically multi-factoral. Progress in diagnosis and treatment, however, has not been matched by etiological understanding. Many questions persist. Where is the confluence of the streams of pathological processes that result in appendicitis? Why does appendicitis show a familial tendency? [1],[2],[3] Why is appendicitis negro-friendly? [4] Why is appendicitis lenient on females? [5],[6] Is there a protective benefit of poor hygiene on appendicitis? [7],[8]

This paper examines the evidence and attempts to provoke inquiry into the factors that contribute to the etiogenesis of appendicitis with a goal to foster understanding of this familiar but still mysterious disease. Perhaps, the mystery is borne out of the fact that we have been looking in the wrong places for answers.

Appendicitis is triggered by a rise in the intraluminal pressure consequent upon obstruction. [9] Bacterial proliferation, luminal mucus elaboration and inflammatory mediators all have roles. The inciting cause may be intraluminal (fecalith, foreign bodies, [10] parasites, [11] barium [12] or colonoscopy [13],[14] ), intramural (tumours, [15],[16] dengue, [17] CMV, [18] HIV, [19] EBV, [20] campylobacteriosis, [21],[22] tuberculosis, [23],[24] salmonellosis, [25] brucellosis, [26] schistosomiasis, [16],[27],[28] amebiasis [11],[29] and enterobiasis [16] ), extrinsic (trauma, [30] genital infections [31] or displaced Cu-T [32] ) or remote (sandstorm [33] and air-pollution [34] ).

Epidemiological studies show stark geographical difference between African and European countries with estimated population incidences per 100,000 of 18 (Ghana), [35] 36.5 (Central African Republic) [36] versus 132 (Spain), [37] 174 (Ireland), [38] 103 (England), [38] 111 (Scotland), [38] and 123 (Wales). [38] In South Korea, the figure is 227. [39] In South Africa, the racial incidence is 5-19 (Blacks) and 215-395 (Whites) per100,000. [4]

This finding mirrors the rates of tonsillectomy among school children in South Africa with a prevalence of 2-3% (Blacks), 8-9% (Colored) and 44% (Whites). [40] A Spanish study found an association between tonsillectomy, adenoidectomy and appendicitis in children. [41]

The finding of an inverse relationship between the length of infant breast-feeding and the risk of subsequent appendicitis in an Italian study [42] when viewed in the light of the fact that African infants tend to be breastfed throughout the first year (unlike their European counterparts) would suggest the protective nature of maternal immunoglobulins in breast milk on intestinal infections.

Rivera-Chavez et al,[43],[44] studied the genetic basis and immunological response to appendicitis. In the first study, [43] they compared the levels of pro-inflammatory (TNF-α, IL-1β, IFN-γ and IL-12) and anti-inflammatory (IL-4, IL-6, IL-10 and IL-1Ra) cytokines in plasma and peritoneal fluids (PF) in histologically proven cases of appendicitis. The first study revealed inverse relationship between the PF and plasma levels of the pro- and anti-inflammatory cytokines. They found that IL-6 and IL-1Ra were the most abundant in plasma and PF with elevations of IL-4 and IL-10 while TNF-α, IL-1β, IFN-γ and IL-12 were low. They observed that Il-6 and IL-10 directly correlated with severity of appendicitis. In the second study [44] on single nucleotide polymorphism in the IL-6 gene, an association was found with the severity of appendicitis even after adjustment for duration of symptoms was made. This finding, and another from Harvard Medical School, [45] lends credence to a genetic basis for appendicitis.

The lower incidence in the female gender may not be unconnected with the well-known fact that females generally mount a less intense metabolic response to trauma and infection than males.

Santosh et al,[46] observed increased numbers of eosinophils in muscle in cases of appendicitis and studied the link between serum eosinophil cationic protein (ECP) levels in cases of appendicitis in comparison to healthy and pathological controls (asthma). Their finding suggests a direct and significant relationship between serum ECP and appendicitis.

A recent epidemiological study [47] of the incidence of appendectomy among monozygotic (3441) and dizygotic (2429) twins in Sweden (comparing those who shared the same environment during childhood and early adulthood and those who didn′t) attributed genetic and environmental factors to account for 30% and 70% of the association, respectively.

Barker et al,[7],[8] observed in two publications in 1988:

"Improvements in hygiene consequent on improved housing, water supplies, and sanitation greatly reduced exposure of young children to enteric organisms, as shown by the fall in childhood mortality from diarrheal disease. It was postulated that this altered the response to subsequent infections in such a way that they cause acute appendicitis". [7]

"We conclude that our findings support the hypothesis that appendicitis is primarily caused by Western housing rather than by Western diet. This would explain the international distribution of the disease which is one of industrialized communities. It explains the rarity of the disease in blacks in South Africa despite their adoption of aspects of Western lifestyle, including low consumption of fiber. It predicts that communities in which children still grow up in conditions of Third World hygiene will experience outbreaks of appendicitis when housing improves". [8]

While Western diet and a mechanistic perspective will continue to be blamed by some of the investigators including world-renowned surgeons, [48],[49],[50] the balance of available evidence suggests that appendicitis is an immunological disease regardless of luminal contents. Appendicitis, like asthma, is the paradoxical consequence of affluence and cleanliness. Immune surveillance eventually leads to antigenic tolerance which, in the case of appendicitis, seems to confer a relative advantage to those living in squalour. Appendicitis, therefore, is evidence that it pays to keep the enemy in sight at all times. Viewing appendicitis in this perspective explains why not all specimens of appendicitis have fecaliths and why not all radiologically detectable fecaliths in the appendix are associated with appendicitis. It further gives insight to the perspective of the so-called catarrhal appendicitis and explains the rarity of appendicitis in the extremes of age on the basis of immaturity and senescence of the immune system.

References

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