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Is Heficobacter pylori of Interest to Ophthalmologists?

1997; Elsevier BV; Volume: 104; Issue: 11 Linguagem: Inglês

10.1016/s0161-6420(97)30035-9

1549-4713

Joel S. Mindel, E. William Rosenberg,

Burkholderia infections and melioidosis

Is Helicobacter pylori of Interest to Ophthalmologists?Acne rosacea is not a disease, but a characteristic combination of skin manifestations.There are probably a multitude of etiologic factors that can produce the hallmark findings of flushing, erythema, and telangiectasia, which can progress to papule and pustule formation, rhinophyma, and ocular involvement.The ocular manifestations include (1) blepharitis, (2) diffuse hyperemic conjunctivitis or a less common, nodular conjunctivitis, (3) episcleritis, and (4) keratitis with painful marginal infiltrates that can erode and become vascularized.Pathologically, the lesions consist of a nonspecific inflammation made up of lymphocytes, plasma cells, epithelioid cells, and giant cells.Helicobacter pylori is a spiral-shaped micro-aerophilic gram-negative bacterium.The organism has been recognized as a causative factor for gastritis and duodenal ulcers and as a risk factor for malignancies of the stomach.Acne rosacea has long been associated with gastritis.In the 1965 edition of Sir Stewart Duke-Elder's Diseases of the Outer Eye, 1 he states, "Digestive troubles have frequently been cited as a causal factor."H. pylori may prove to be a missing link.How might H. pylori, residing in the stomach, cause acne rosacea?H. pylori is known to produce the enzyme urease.Urease, which does not normally occur in humans, breaks down urea to ammonia and C0 2 • The ammonia raises the pH of the adjacent gastric fluids, protecting the bacterium from their acidity.However, the elevated pH also stimulates release of the peptide hormone gastrin from the gastrin-producing G-cells of the stomach into the portal circulation.Gastrin acts locally to both stimulate gastric parietal cells to secrete hydrochloric acid, thereby relowering the pH of the gastric fluids, and to vasodilate the mucosal layer.Gastrin reaching the systemic circulation could produce vasodilation of the skin and the other manifestations of acne rosacea.There is some evidence that raises this concept above pure speculation: ( 1) high incidences of H. pylori serum antibodies (80%) and of H. pylori-positive gastric biopsies (84%) are found in patients with acne rosacea 2 ;(2) serum gastrin levels are elevated in patients with peptic ulcers, and these levels become markedly reduced after successful eradication of H. pylori 3 ;(3) injections of gastrin produce flushing 4; and (4) both H. pylori and acne rosacea respond to the same antimicrobial agents, e.g., tetracycline.It should be noted that carcinoid tumors, which secrete vasodilating neurotransmitters such as histamine, are also associated with flushing, telangiectasia, and the other stigmata of acne rosacea.There are some weaknesses in the preceding rationale.Consistent evidence does support the beliefs that H. pylori infection results in elevated gastrin blood levels and that eradication of H. pylori reduces gastrin blood levels.Why then does H. pylori-associated gastric disease not always produce acne rosacea?Perhaps it is because different strains of H. pylori have different biochemical characteristics and pathogenicities. 5It is not known whether infection with certain strains of H. pylori correlates with higher levels of circulating gastrin.A further complicating factor is that serum gastrin levels may not always predict the severity of acne rosacea, because the hormone can exist in different forms with different activities.The typical form of gastrin has a molecular weight of about 2100 daltons (d).Larger and less pharmacologically active forms are found in some of the gastrin-secreting tumors that produce the Zollinger-Ellison syndrome.These "big gastrins," have molecular weights of about 3900 d.Their relative lack of activity may also explain why the Zollinger-Ellison syndrome is not uniformly associated with acne rosacea.A smaller form of gastrin, "minigastrin," exists, and can be found in some normal subjects, as well as in patients with gastrinomas and pernicious anemia.Further, sulfonated and nonsulfonated subtypes exist for each form of gastrin.A second weakness of the theory concerns the effectiveness of topically applied antibiotics, such as metronidazole-how could they affect H. pylori in the stomach?An intriguing speculation is that the gastrin flush results from increased levels of the potent vasodilator nitric oxide in the skin.Tetracycline inhibits expression of nitric oxide synthesis. 6Perhaps other antibiotics do the same.A third weakness arises regarding antacids.Some patients take multiple calcium carbonate tablets on a daily basis as a calcium supplement.Why do they not produce or aggravate acne rosacea?The carbonate, like ammonia, raises the gastric pH, and the calcium is an additional gastrin secretion stimulant.And, finally, how does gastrin, a vasodilator, produce the painful scleral nodules and corneal infiltrates of ocular acne rosacea?It may be that the gastrin-acne rosacea theory is imperfect or wrong, but eradication of H. pylori is effective.