Tag Archives: white cell

Bladder and bowel, Intimate issues

Detecting and preventing urinary tract infections

Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress. I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.

Urinary tract infection and disease progression

Infections, both viral and bacterial, are a known trigger of relapse. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce urinary tract infections. You can do this in several ways, such as increasing the frequency of ISC.

Drinking plenty of liquids to flush the bladder reduces infection rates. Changing the pH of your urine by drinking citric acid (citro soda or lemonade) also helps. Making your urine more alkaline or more acidic may work, depending on the bacterial species colonising your bladder. Cranberry extract, for example, contains proanthocyanidins, a substance that reduces bacterial colonisation of the bladder. (You need to use the extract and not the juice because the proanthocyanidin concentration in the juice is too low to have an effect.)

Another very effective option (but infrequently used) is a bladder instillation with a liquid containing sodium hyaluronate (Cystistat), which replaces the glycosaminoglycan layer, or glycocalyx, of the bladder wall. This makes it difficult for bacteria to stick to the bladder wall to cause infections and is one way of preventing bacterial biofilms, or slime, from forming. Biofilms are a significant problem because they prevent antibiotics from reaching the bacteria to kill them and act as a breeding place for recurrent infections.

Urinary antiseptics are antibiotics, given in low concentrations, that may help to reduce urinary tract infection rates. They are typically administered in tablet form; they work by being concentrated by the kidneys and making the urine antiseptic, which helps to prevent or treat urinary tract infections. The agents I use currently are trimethoprim, cephalexin and nitrofurantoin. (Methenamine, another urinary antiseptic, is not readily available in the UK due to supply issues.) Cycling their use, every 3 ̶ 4 months, prevents the bladder bacteria from becoming resistant to a specific antibacterial. We have stopped using nalidixic acid and other drugs in the oxolinic acid class because they are associated with tendonitis and tendon ruptures.

Interpretation of urine dipstick results

Early detection of urinary tract infections (UTIs) means that they can be treated promptly to prevent symptomatic infection or complications such as pyelonephritis (kidney infection) and septicaemia (a common cause of death in people with advanced MS). Dipstick testing can be carried out at home, as part of self-management of your MS. I recommend doing dipstick monitoring once or twice a week, not daily. If positive, you must drop off a clean urine sample to your healthcare provider for proper laboratory analysis (microscopy, culture and sensitivity). This is to confirm the presence of a UTI, to culture and isolate the bacteria causing the infection, and to test the sensitivity of the bacteria to antibiotics. You must send your urine specimen for analysis before you start antibiotics. 

For UTI monitoring, the leukocyte and nitrite tests are the most important, with backup from the protein, blood and pH tests. The guidance in the table below explains how to interpret some of the key dipstick test results relevant to UTIs and what the different readings on a typical urine dipstick mean. You need to wait up to 2 minutes to read the results; if in doubt, take a picture of the test strip with your mobile phone and email it to your HCP for interpretation.

Dipstick results

Guidance to help you interpret the dipstick results relevant to urinary tract infection (UTI). You should wait for up to 2 minutes before reading the results (2 minutes for leukocytes, at least 60 seconds for other results shown here).
*If you have been treated with alemtuzumab, new-onset proteinuria in the presence of blood may indicate Goodpasture’s syndrome, a rare autoimmune complication of alemtuzumab treatment. Please consult your HCP.
UTI, urinary tract infection.

The image below shows what the different readings on a typical urine dipstick mean; the readings for white blood cells, nitrite, protein, pH and blood are important for detecting the presence of a UTI (more information is in the Table above). Further details about readings for urobilinogen,  specific gravity, ketone levels, bilirubin and glucose are available in my newsletter entitled How to interpret a urine dipstick result.

An example of results from a urine dipstick test; the readings most relevant to interpreting urinary tract infections are white blood cells, nitrite, protein, pH and blood. Information about additional results from dipstick testing are available in my newsletter entitled How to interpret a urine dipstick result.

DMTs, Treatment strategy

How immunosuppressed am I?

Do you understand the difference between short-term intermittent and long-term continuous immunosuppression? Here we address another of the key questions to consider before deciding on a specific disease-modifying therapy (DMT).

Key points

  • Immunosuppressive disease-modifying therapies (DMTs) reduce the immune system’s effectiveness.
  • It is important to weigh up the benefits and risks of short-term versus continuous immunosuppression.
  • Non-selective DMTs suppress the adaptive and innate immune systems; selective DMTs do not affect the innate immune system and are thus associated with a low risk of bacterial infections.
  • The implications of immunosuppression need to be considered within the context of other health and lifestyle factors.

Which DMTs cause immunosuppression?

A useful way of thinking about DMTs is based on whether they are immunosuppressive. Broadly speaking, an immunosuppressive is any DMT that reduces the immune system’s activation or effectiveness. 

From a regulatory perspective, for a drug to be classified as immunosuppressive, it should: 

  • cause significant lymphopaenia or leukopenia (reduced white cell counts)
  • be associated with opportunistic infections (infections that don’t occur in people with a normal, healthy immune system)
  • reduce antibody and/or T-cell responses to vaccines 
  • increase the risk of secondary malignancies. 

Based on the above criteria, the interferon-beta preparations and glatiramer acetate are immunomodulatory rather than immunosuppressive. Teriflunomide is also an immunomodulatory therapy with the potential, albeit small, to cause immunosuppression. In real life, however, very few people with MS treated with teriflunomide develop significant lymphopaenia or leukopenia; if they do, we tend to stop the drug. The other licensed DMTs are immunosuppressive to a greater or lesser degree. 

Short-term versus continuous immunosuppression

The duration and intensity of immunosuppression further determine the risks. Short-term or intermittent immunosuppression associated with an immune reconstitution therapy (IRT) front-loads the risks, which decrease substantially once the immune system has reconstituted itself. In comparison, long-term continuous or persistent immunosuppression, which occurs with most maintenance DMTs, accumulates problems over time, particularly opportunistic infections and secondary malignancies.

Live vaccines are, in general, contraindicated in patients on continuous immunosuppressive therapies. However, someone with MS on an IRT who has reconstituted their immune system can tolerate and respond to live vaccines. The benefits of administering live vaccines always need to be balanced against the risks of the vaccine.

How immunosuppressed are you table updated format 180625 SS

The main characteristics of continuous persistent and short-term (intermittent) immunosuppression. Modified from Giovannoni, Curr Opin Neurol.1
AHSCT, autologous haematopoietic stem cell transplantation; PML, progressive multifocal leukoencephalopathy.

Selective versus non-selective immunosuppression

Immunosuppression that accompanies DMTs may be selective or non-selective. Non-selective therapies deplete and/or suppress both the adaptive immune system (T cells and B cells) and the innate immune system (monocytes, neutrophils and natural killer [NK] cells). Alemtuzumab, AHSCT (autologous haematopoietic stem cell transplantation) and mitoxantrone are non-selective and are therefore associated with acute bacterial infections such as listeriosis, nocardiosis and cytomegalovirus reactivation. In comparison, anti-CD20 agents (ocrelizumab and ofatumumab) and cladribine are selective, do not affect the innate immune system and are therefore associated with a low risk of acute bacterial infections. 

How immunosuppressed are you_MET vs IRT_2 Dec 2024

Classification of disease-modifying therapies for relapsing forms of MS. Modified from Giovannoni, Curr Opin Neurol.1
AHSCT, autologous haematopoietic stem cell transplantation.

Other considerations

Please note that the implications of immunosuppression are not black and white but interact with other factors such as:

These factors have been highlighted during the COVID-19 pandemic, particularly in relation to the risk of severe COVID-19 and the variations in vaccine responses among people with MS (including waning of the immune response).

It is important to realise that we can derisk (reduce the risk of) some complications associated with long-term immunosuppression and the use of DMTs. Please see the post entitled How can I reduce my chances of adverse events on specific DMTs?

References

  1. Giovannoni G. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol 2018;31:233 ̶ 43.