0.9 0.8- 0.7- I 0.6- 0.5- j c Q. g 0.4- o <u 0.3- 0.2- Achalasia DOS/Nutcracker/ Control Hernia vigorous achalasia Figure 7.1.1
Peripheral blood eosinophil counts in controls and patients with reflux disease or motility disorders of the oesophagus.
Discussion
It is possible to stain eosinophils in the blood using specific stains and then to count them in special counting chambers. However this is time consuming and not readily applicable to clinical practice. Therefore the routine, automated counting method used at East Birmingham Hospital was used for this study. The finding of a significantly elevated blood eosinophil count in the motility disorders would have been of great interest. If it had been restricted to those cases with associated AP eosinophilia then it would have been a useful marker of an eosinophil association for the disorder. On the other hand, if significantly elevated eosinophil counts were found in all the motility disorders it would have suggested that eosinophils were involved in the pathogenesis in all cases and that the lack of tissue eosinophils in AP might be a result of sampling at inappropriate times in the development of the disease or at a relatively uninvolved site in the oesophagus.
However neither of these were found. The vast majority of patients had
eosinophil counts within the normal range for the laboratory. This does not mean that eosinophils are not involved in the pathogenesis of the disease. Although asthma is commonly associated with eosinophilia it is well established that eosinophil counts can be normal in asymptomatic asthmatics and some patients during severe attacks can demonstrate eosinopenia (Wardlaw and Kay 1987)
Conclusions
The peripheral blood eosinophil count is not pathologically raised in reflux
disease, achalasia or the other motility disorders DOS, nutcracker oesophagus and vigorous achalasia.
7.2 SERUM IGE LEVELS IN OESOPHAGEAL DISEASE.
Introduction
In the normal individual the serum level of IgE is low relative to the levels of the other immunoglobulins. However in patients who are atopic or with parasitic disorders the levels of IgE can be markedly elevated in the blood. This IgE can be passively bound to mast cells in the tissues, and when exposed to the specific antigen, crosslinking of IgE molecules occurs and mast cell degranulation is initiated. This can then result in release of vasoactive mediators and chemotactic factors. Eosinophils are often found in the resultant infiltrate.
In asthma, serum IgE levels can be normal or raised. Although the tissue
infiltrate of eosinophils is similar irrespective of the serum IgE, there are thought to be two separate mechanisms underlying the asthmatic tissue response. One is IgE dependent and the other is not.
In a previous chapter increased numbers of cells staining positively with an anti- IgE antibody have been found in DOS and vigorous achalasia. Large numbers of cells staining with anti-IgE antibody have also been found in a study of the rectal mucosa in patients with proctitis (Heatley et al. 1975). However, serum
immunoglobulin E levels were within the normal range for the majority of patients.
Serum IgE was measured in a variety of oesophageal disorders to assess how frequently serum IgE was elevated in the motility disorders of the oesophagus. In those cases with marked elevation of serum IgE a radioallergosorbent test (RAST) was performed on the serum looking for IgE antibodies directed against common food allergens.
Methods
The patients studied included 10 controls, 14 patients with reflux disease, 17 patients with achalasia and 28 patients with a diagnosis of DOS, vigorous achalasia or nutcracker oesophagus. Their clinical details can be found in Appendix 4. Informed consent was obtained from all the subjects.
Blood was obtained by peripheral venepuncture and placed in plain glass tubes. It was then spun at 25,000 rpm for 5 minutes and the serum pipetted off. It was
frozen to -70^C and stored in a batch prior to analysis. Analysis of serum IgE using a standard radioimmunoassay (using the Pharmacia CAP system) and the specific RAST tests (Pharmacia) were performed in the Regional Immunology Dept., Birmingham Heartlands Hospital. RAST testing was performed on the following common food allergens: cod, egg, milk, wheat, nuts and soya.
Results
The results of the serum IgE estimations are detailed in Appendix 6 and displayed graphically in Figure 7.2.1. The upper limit of normal for the laboratory is 200 KU/1. It can be seen that all the control results are within the normal range. In 7 of 28 patients (25%) in the DOS/vigorous achalasia group, 2 of 16 in the
achalasia group (12.5%), and 4 of 14 patients in the hernia group (28.5%) IgE levels were above the normal range. Statistical analysis using the Mann Whitney U test showed no difference in IgE levels between the vigorous contraction abnormalities and either control patients (P= 0.39) or patients with hiatus hernia (P= 0.88).
In table 7.2.1 those patients who had both biopsies and serum IgE estimations are detailed. Although there was no statistically significant correlation between blood IgE levels and AP IgE positive cells, it should be noted that 3 of the 5 cases of DOSWigorous achalasia who had high serum IgE levels (195-535 KU/1) had increased numbers of both AP eosinophils and AP IgE-positive cells in AP. Two of the hernia patients wtih biopsies had raised IgE levels. In neither of these were AP eosinophils raised and in one, a patient with repeated attacks of anaphylaxis, there was a raised level of AP IgE-positive cells.
Table 7.2.2 details the results of the RAST testing on those samples obtained from patients with very high immunoglobulin E levels. In the patients studied, no clear evidence of an IgE response to these common food allergens emerged.