Chronification of PsA

Question

Dear Expert Team,

first of all, many thanks for your answer to our previous question, on how to deal with PsA antibodies.

Could you please briefly explain to me the process leading to chronic colonization with Pseudomonas Aeruginosa? It somehow seems like there are differing definitions… What parameters are necessary? And what is the approximate time span during which PsA becomes chronic if one has gotten maximum therapy early on?

How does one explain the fact that there is not a single patient under 18 years of age with chronic PsA in Denmark, whereas in Germany many children already have it?

Thank you for your answer.

Answer

Dear questioner,

yes, you are completely right – the definition of chronic PsA is indeed difficult, and even though there are a number of different definitions, none of them is undisputed. Therefore, you need to pick a definition that seems useful to you from the many that are available.
There are European guidelines ("Antibiotic therapy against P. aeruginosa in cystic fibrosis: a European consensus" by Döring et al. 2000) which distinguish between the terms "colonization" (presence of P.aeruginosa without direct (inflammation, fever) or indirect (specific antibodies) signs of infection and tissue damage) and "infection" (presence of bacteria with direct or indirect signs of infection). Therefore, the difference between chronic colonization and chronic infection is characterized by the presence or absence of direct and indirect signs of infection. Both terms have in common the presence of P. aeruginosa in the bronchial tree for at least 6 months, based on at least 3 positive cultures with at least one month intervals between them. Chronic infection can also be diagnosed on the basis of a positive antibody response in at least two examinations for patients who do not expectorate and present negative bacterial cultures.

I would define the contact of the respiratory system with Pseudomonas as follows:

I would call the first evidence of Pseudomonas in the sputum or throat swab without concurrent proof of an increased number of Pseudomonas antibodies “initial colonization.” Here, eradication therapy is successful in most cases.

If, however, there is proof of an increased number of antibodies, this is considered an infection or inflammation; this means that not only is there evidence of Pseudomonas, but it has already led to an inflammatory reaction in the respiratory system, which can be seen from the formation of antibodies.

A chronic Pseudomonas infection is at hand if, even after an antibiotics therapy, Pseudomonas is still detectable, along with an increased number of antibodies. There are, however, a few patients who do not show an increase in antibodies despite a long-term colonization with Pseudomonas. Here, you would speak of a chronic colonization.

Your second question about how long it takes for a colonization to turn into an infection is hard to answer. It is quite possible for this to happen within 3 months; however, in some rare cases it can take several years. European guidelines state on this topic (Döring et al 2004, “Early intervention and prevention of lung disease”): "After introduction of early intensive treatment the probability of still not having developed chronic PA infection 7 years after the first isolation was above 80%." Therefore it is recommended to start eradication therapy right after the initial evidence of Pseudomonas.

As for your third question: There are indeed hardly any children with chronic Pseudomonas in Denmark anymore. However, this does not mean that there is no colonization at all. Since most patients in Denmark report to the CF center on a monthly basis, one could imagine that eradication therapies are carried out earlier. In this way, it might be possible to prevent the transition from colonization to infection more frequently as the approach is more consequent. Another reason for the different data from Denmark might also be the definition of a chronic infection with P. aeruginosa there: in Denmark, a chronic P. aeruginosa state is defined as 5 Pseudomonas positive cultures in succession out of 6 cultures (sputum or throat swab). So if the same definitions would be used anywhere, the data might look different.
I hope my answer will help clarify this difficult topic for you a bit.

Best wishes

E. Rietschel

28.04.2009