Introduction
The breed of Soft Coated Wheaten Terriers (SCWT) seems to be specifically prone to develop PLE and/or PLN. PLE is defined as a non-selective loss of serum
proteins (albumin and globulin) via the small intestine. It is usually caused by primary small intestinal lymphangiectasia or secondary to inflammatory bowel disease. However, its specific cause
in SCWT is unknown. PLN is characterized by a loss of albumin from the kidney.
An estimated percentage of approximately 10% of dogs of this breed in the United States and an unreported percentage of SCWTs in the UK develop PLE and /or PLN.
The first SCWT with PLE in the U.K. was published by Melville et al. in 2004. Littman et al have performed a pedigree analysis over four generations of SCWT and found a common male
ancestor attributed to the affected dogs. This suggests a genetically inherited condition, but the mode of inheritance remains unknown.
Studies in the US reported that these syndromes affect middle aged to older dogs (4-6 years) with a predisposition for females. PLE and PLN are devastating diseases
associated with severe weight loss, inappetence, diarrhoea, vomiting, polyuria/polydipsia (increased drinking and urination), ascites and dyspnea because of pleural effusion and peripheral oedema.
Mesenteric lymphadenopathy, thromboembolic disease and cardiac abnormalities can also be seen in some cases. Clinical signs of PLE may arise earlier than signs of PLN. PLE and PLN are chronic and
often fatal in SCWT. Prognosis is poor with median survival times of a few months (five months for PLE and two months for PLN) after the diagnosis.
Due to unspecific clinicopathological parameters of the disease and its poor prognosis, early diagnosis of the disease is crucial for the dog’s health and
could help eradicating the disease through the use of breeding programmes. Thus, it has been suggested that pANCA might be an early serological marker for PLE/PLN in this breed.
Recently, some studies regarding pANCA and PLE/PLN in Soft Coated Wheaten Terriers (SCWT) have been carried out. In a study with SCWTs and SCWT-Beagle crossbreed
dogs affected with PLE/PLN from a colony at North Carolina State University , it was estimated that the sensitivity and specificity of the pANCA test for the diagnosis of PLE/PLN in this breed was
95% and 80%, respectively (Allenspach et al American Journal of Veterinary Research, 2008). Therefore, pANCA seemed to be strongly associated with PLE and PLN in SCWT. Moreover, it was reported
that the first positive result for pANCA was seen 2 to 3 years before the onset of hypoalbuminaemia (decreased blood albumin levels), which indicates that it may be a useful early non-invasive test
for predicting which animals will develop PLE/PLN. However, since almost all dogs of that study (18/21) ended up having the disease, further studies are needed in a larger population of dogs of this
breed.
A previous cross-sectional study in healthy SCWT performed in the UK found that the prevalence of pANCA in this breed was 20.7%. Such a remarkable prevalence of
pANCA status is not considered as normal in a healthy dog population, as these auto-antibodies are considered to be increased in auto-immune diseases. It was therefore, considered possible that a
proportion of these dogs was likely to develop PLE/PLN later on in their life. Therefore, since then, a longitudinal study was performed, in order to evaluate the clinical usefulness of the pANCA
test for the diagnosis of PLE/PLN and the importance of the disease in this breed in the UK .
Results
Prevalence of PLE/PLN in SCWT in the UK
During the study period, over half (57/103 or 56%) of the dogs reached the age where disease onset is likely to occur (4-6years). Two dogs of the longitudinal study
population (2/103) were affected with PLE and/or PLN. Both dogs were detected as pANCA negative. Three more cases have been reported at the Queen Mother Hospital at the Royal Veterinary College.
Blood has been collected from 2 of them and one was found to be pANCA positive.
Therefore, we estimated the incidence of PLE/PLN in the SCWT in the UK to be 2% (CI 95%, 0.002 to 0.068). This is a very positive finding, as it means that not
very many dogs are affected at this time-point. It is likely that the awareness of the disease was raised among breeders over the last few years and that this has contributed to less inbreeding of
affected dogs.
Prevalence of pANCA in healthy SCWT in the UK
From the longitudinal study 14 out of 103 (14%) dogs were found to be pANCA positive. From the dogs that participated in all of the sampling sessions, 1 (0.9%)
had repeatedly tested pANCA positive and 27 (26%) tested negative at all time points. Forty five out of 103 dogs (44%) were detected as pANCA negative and 4 (3.9%) as pANCA positive at the times
the dogs participated in the sampling sessions. Fourteen (13.6%) converted from negative to positive, six (5.8%) from positive to negative and six (5.8%) changed their pANCA status more than once
over the study period. Total percentage of dogs with fluctuation of pANCA status was 25% (see Table).
Therefore, a remarkable percentage of dogs had changed their pANCA status over the study period at least once. The phenomenon of seroconversion of pANCA has also
been noticed previously in other studies in dogs using immunofluorescence and it seems to be due to variable antibody levels in the blood at each time the dog is tested. In order to determine the
true pANCA status of a dog, it was important that all dogs were retested as many times as possible within the study period. As it was not feasible for all the owners to bring their dogs for all the
sampling sessions, we have some missing pANCA data in our longitudinal study with SCWT, which might have affected our results.
Table: Proportion of dogs with fluctuations in their pANCA status
pANCA fluctuation |
Number of dogs |
| negative at all samplings |
27 (26%) |
| negative at the times they have participated |
45 (44%) |
| positive at all samplings |
1 (0.9%) |
| positive at the times they participated |
4 (3.9%) |
| Seroconverted from negative to positive |
14 (13.6%) |
| Seroconverted from positive to negative |
6 (5.8%) |
| Seroconversion of pANCA status more than once |
6 (5.8%) |
| Total number of dogs |
103 |
During the longitudinal study period approximately 2% (2/103) of the dogs had serum albumin concentrations (range 17.1–27.9) below the reference range,
74% (76/103) within the reference range (28-39g/l) and 24% (25/103) above (range 39.2-72.1gl), (see Figure). An important percentage of dogs had albumin concentration above the reference range.
This might be due to stress, dehydration or consumption of recent meal. Furthermore, it is possible that the reference range of albumin concentration in SCWT might be higher than in other breeds
of dogs, as the population of dogs making up the reference range at the Royal Veterinary College did not include many SCWT.
Figure: Proportions of dogs with albumin concentrations below,
within and above reference range (28-39g/l)
No statistically significant association was observed between a pANCA positive status and dogs affected with PLE/PLN. Sensitivity of pANCA test for diagnosing
PLE/PLN was calculated at 25% and specificity 84%. However, the low prevalence of PLE/PLN in SCWT in UK makes it difficult to evaluate the reliability and the accuracy of the pANCA test for these
syndromes. Since 18% (19/103) of the dogs in this longitudinal study were in the age range of the disease onset by the end of the study, it is possible (although not hoped for!) that some of these
will still develop PLE/PLN in the future. Thus, clinical information on all dogs included in the study, regardless of their pANCA status, should ideally be collected, in order to reach a more scientifically
reliable result.
It will be of major importance for our project, to contact us if there are any changes in your dog’s health. Questionnaires should be completed and sent to
us approximately every 6 months.
In addition, regardless of the results of this study, a wealth of clinical and pedigree information on healthy and affected dogs of this breed has been collected
over the study period. Consequently, this project could be the basis for genetic studies regarding PLE/PLN in SCWT in the UK . Moreover, the higher prevalence of PLE/PLN in USA compared to a lower
prevalence in UK further supports that different environmental factors may play a role and may affect the prevalence rate in different countries.
We would like to thank everyone involved very much for participating in this study and the UK Kennel Club for generous funding of the study.
Best Regards,
Karin Allenspach, Barbara Wieland,
Anna Eleonora Karagianni and the RVC team
September 2010
If your dog participated in this project and has since died, Dr Allenspach would like to hear from you. Please Contact the Project Coordinator for Dr Allenspach's contact details.