Does helicobacter pylori play a role in upper respiratory tract inflammation? A case report.

Abstract

Persistent isolated inflammation of the sphenoid sinus, an entity that is not diagnosed very often, poses a challenge to clinicians and researchers alike. Its features tend to suggest that its etiopathogenesis is different from that of more common forms of chronic rhinosinusitis. We report the case of a 54-year-old woman who had a history of distressing chronic postnasal drip and a globus sensation with opacification of the sphenoid sinus. She was diagnosed with gastroesophageal reflux, and Helicobacter pylori was detected in her gastric contents and in the inflamed mucosa of the sphenoid sinus, as well. Complete symptom relief was achieved only after she had undergone surgical sphenoidotomy and treatment with anti--H pylori medication. We discuss the potential for this ubiquitous gastric bacterium to play a role in at least some forms of chronic sinonasal inflammation.

Introduction

Helicobacterpylori is a human gastric bacterial pathogen that has been associated with chronic gastritis, peptic ulcer, and, presumably, gastric malignancy. (1) The possibility that this organism may colonize epithelia other than that of the stomach is debatable. In 1997, Veerman et al reported that H pylori had been detected at various sites in the oral cavity. (2) This finding lent support to the idea that H pylori might be transmitted orally. It also raised a question as to whether this microorganism is capable of inducing pathology at sites other than the stomach.

We present a case in which the presence of H pylori was documented in the posterior nasal cavity of a patient who had chronic inflammatory sinus disease. We discuss the possibility of an etiopathogenic role for this microorganism in extragastric inflammation.

Case report

A 54-year-old woman sought care for persistent postnasal drip and a globus sensation. Findings on the otolaryngologic examination were unremarkable. She was prescribed standard maximal medical treatment for suspected rhinosinusitis, which entailed 2 weeks of oral amoxicillin/clavulanate and 8 weeks of topical steroid therapy.

When the patient failed to respond to medical therapy, computed tomography (CT) of the sinuses was ordered. CT demonstrated a total opacification of the right sphenoid sinus with an isodense soft-tissue signal (figure 1). No bony erosion or sign of expansion was noted, and no pathology was seen in any other sinus. T2-weighted magnetic resonance imaging (MRI) displayed the pathology with bright signal intensity, a finding that is consistent with a benign inflammatory origin. Because her history included minor symptoms of dyspepsia, an ambulatory 24-hour double-probe esophageal pH monitoring study was performed. (3) This test detected a normal acid-exposure time at the distal catheter, which was located 5 cm above the lower esophageal sphincter; however, some reflux episodes were diagnosed at the proximal catheter located at the hypopharynx (figure 2).

[FIGURE 1-2 OMITTED]

The patient was prescribed a 2-month course of omeprazole at 20 mg twice daily, but she reported no significant improvement. Another MRI obtained at this time showed that the sphenoid sinus pathology had persisted and had been unaltered by drug treatment. She was then scheduled for surgery.

An endoscopic sphenoidotomy was performed under general anesthesia, the sinus being directly opened through the sphenoethmoid recess. Abundant, whitish, chalk-like, intraluminal debris was collected and sent for histologic and microbiologic examinations. Edema of the mucosal lining of the sinus was also detected, and a sample was taken for histopathology. Two biopsy specimens were obtained specifically for a polymerase chain reaction (PCR) assay for H pylori. (1) One sample was obtained from the mucosa of the sphenoethmoid recess before the sinus was entered, and the second was taken from the mucosal lining of the sinus itself. A large opening into the sphenoid sinus was left at the end of the procedure to ensure sinus self-cleansing and aeration and to allow for postoperative endoscopic observation.

The subsequent examination of the histopathologic materials revealed the extramucosal presence of numerous fungal hyphae in the mucin layer. This finding was compatible with the suspected intraoperative diagnosis of a fungus ball. Unfortunately, and possibly because of the complex requirements for culturing, microbiologic analysis failed to identify the fungal specie or species involved. The PCR assay, however, was positive for H pylori at both the sphenoethmoid recess and the intrasinus sites (table).

Postoperatively, the patient was prescribed a short-term (2 week) course of oral cefuroxime. At follow-up, she reported that she was markedly improved, although she had not experienced a complete resolution of her symptoms. Sinus CT was not obtained at this early postoperative stage, but nasal endoscopy showed that the sinus mucosa was still edematous despite repeated saline sinus irrigations. Because her dyspepsia continued to bother her to some extent, she was further submitted to esophagogastric endoscopy, which detected chronic gastritis and reflux esophagitis. The PCR assay for H pylori in the gastric mucosa specimens was positive.

Only after an appropriate anti--H pylori treatment regimen (including recommended antibiotic therapy) a few months after surgery did all her aerodigestive symptoms completely resolve. MRI 6 months postoperatively revealed that the previously persistent inflammation of the mucosal lining of the sphenoid sinus was in remission (figure 3).

[FIGURE 3 OMITTED]

Discussion

For some years, a body of evidence, mostly anecdotal, has accumulated in the otolaryngology literature that implicates gastroesophageal reflux as a critical pathogenic factor in a number of ENT conditions, including laryngeal, pharyngeal, and even rhinologic pathology. (3) Animal research has shown that pepsin is probably the primary component of injury to the respiratory mucosa in the regurgitated gastric contents. (3) Although H pylori is present in the stomach in approximately half of the world's population (1) and is presumably able to seed the respiratory tract in cases of reflux, the hypothesis that this microbial agent plays some role in reflux-induced upper respiratory tract disease has seldom been considered. A study published by Cellini et al in 1995 failed to identify H pylori in the nasal mucus of H pylori--positive dyspeptic patients. (4) However, these authors used a less-sensitive detection method (microbiologic culture) than we did (PCR).

In the digestive system, H pylori exhibits specificity in its tissue targeting. (1) It attaches exclusively to gastric mucosal cells because they have specific receptors, but it is unable to target, for instance, the intestinal epithelium, which does not have these receptors. (1)

In the oral cavity, which is thus far the only other site where H pylori has been detected, evidence suggests that the salivary mucins may act as receptors for the local adhesion of the bacterium. (2) To be able to develop any pathogenic activity in the respiratory mucosa, H pylori would also have to specifically bind to receptors, an event that until now has not been documented. Also, the oral adhesion of H pylori is apparently a transient step toward gastric colonization. No data exist to support the idea of a permanent oral reservoir of H pylori. Therefore, the recovery of the bacterium in the mouth is seemingly intermittent, induced by recurring gastroesophageal reflux. And as far as we know, H pylori does not cause specific oral disease.

With that in mind, we advise a cautious interpretation of our reported evidence of the presence of H pylori around the sinus ostium and inside the sphenoid sinus in a patient with isolated primary sphenoiditis. In view of the fact that H pylori is ubiquitous in the digestive tract and that gastroesophageal reflux is so common, H pylori may perhaps be just an innocuous bystander in either healthy or diseased upper respiratory tract mucosa. Its presence may simply go undetected because of a lack of an educated suspicion.

However, the possibility of a pathogenic role for H pylori in extradigestive tissue should not be dismissed too lightly, as its role in gastric tissue injury is known to be devastating in some cases. In our patient, we would assume that the sphenoid sinus was the site of an inflammatory process similar to an H pylori gastric infection, with chronic superficial inflammation, mononuclear cell invasion, and neutrophilic infiltration of the epithelium. (1) (The fungus ball would then most likely be a secondary phenomenon resulting from altered sinus physiology.) One can even speculate as to whether H pylori would be the true and sole pathogenic mechanism behind respiratory reflux pathology or eventually act as a coadjuvant to the pepsin-induced inflammation. Alternatively, this microorganism could exist in the nose in an unculturable inactive coccoid state, only to initiate proliferation and cause disease under specific circumstances. This possibility would perhaps explain the failure of non-PCR modalities to identify H pylori. (4)

However, all these hypotheses await scientific validation. In particular, we do not know if a specific receptor for H pylori exists in the posterior nose; if one does, we would need to establish whether the bacterium, once it is attached to the epithelium there, is capable of developing pathogenic activity. Until more biologic studies and large clinical series are reported, the causality between H pylori and sinus disease inflammation simply cannot be established. In the meantime, our findings in this particular case do seem to suggest that in patients with isolated sphenoid sinus disease, testing and treatment for H pylori may perhaps merit at least some clinical consideration.

References

(1.) Dunn BE, Cohen H, Blaser MJ. Helicobacter pylori. Clin Microbiol Rev 1997;10:720-41.

(2.) Veerman EC, Bank CM, Namavar F, et al. Sulfated glycans on oral mucin as receptors for Helicobacter pylori. Glycobiology 1997; 7:737-43.

(3.) Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991;101 (4 Pt 2 suppl 53): 1-78.

(4.) Cellini L, Allocati N, Dainelli B. Failure to detect Helicobacter pylori in nasal mucus in H pylori positive dyspeptic patients. J Clin Pathol 1995;48:1072-3.

From the Department of Otorhinolaryngology, Hospital de Pulido Valente, Lisbon.

Reprint requests: Dr. R Borges Dinis, ORL Department, Hospital de Pulido Valente, Alameda das Linhas de Torres 117, 1769-001 Lisbon, Portugal. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

Table. Polymerase chain reaction detection of H pylori in the two
nasosinusal biopsy specimens

                                  Cutoff    Reference
Site                   Result     index *   value *

Sphenoethmoid recess   Positive   5.20      <1.00
mucosa

Sphenoid sinus         Positive   >12.0     <1.00
mucosa

* The cutoff index indicates the number of times a result is positive
with regard to the reference value that is used.