We are cruising in an Airbus A380 at 36,000 ft, at nearly 570 mph, about half-way through a 14-hour flight from Sydney to Dubai. Unusually, the flight is jammed (apparently, Aussies head to Dubai for Easter), and I am confined to an inner row seat in the middle row of the cabin. Economy of course. I have already burned through three movies, and my over-air conditioned eyes are exhausted by the excessive photons, not to mention the sleep deprivation. I decide to switch my dwindling attention to selecting a topic for the current column. I could look into deep vein thrombosis perhaps (which I have convinced myself a likely victim), or perhaps the long-term effects of air travel on circadian rhythms? As I begin to dose off, the answer reveals itself through the fog of exhaustion. Bladders. Multi-coloured bladders, floating majestically over terracotta sands. I blink to clear the daze, and realise I’m half sleep-watching an advert for hot-air ballooning in OZ. Inspiration received!
Interstitial cystitis/bladder pain syndrome
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition where pain is experienced as the bladder fills, and pain relief comes with bladder emptying. This often results in the urgent need to urinate or to urinate frequently (up to 60 times a day by some reports). IC/BPS is very common and affects women more than men (best guesses range from 3:1 to over 10:1), and is often seen with other conditions such as fibromyalgia and IBS.
Clearing the waters
Until recently, the terminology surrounding IC/BPS was varied, nomadic and confused, which hampered doctors in effectively diagnosing and treating the condition. Thanks to the hard working people of the International Continence Society and the International Urogynecological Association though, IC/BPS has now been more accurately subtyped under the umbrella of Chronic Pelvic Pain Syndrome (CPPS) (Doggweiler et al 2016). The committee’s report provides detailed symptoms, signs, evaluation approaches and designations for nine organs systems in detailing CPPS, and it is well worth the read, even if a little cumbersome to navigate (Cox et al 2016 provides a more user friendly version focused on IC/BPS). Aligning how we diagnose the condition will pave the way for better assessment and comparison of how treatments are working.
Features of IC/BPS
The cause of IC/BPS is not known, but several features are recognised. Inflammation is a cornerstone feature, and Hunner lesions (patches of broken skin on the bladder wall) or glomerulations may also be visible during cystoscopy. Alterations in the glycosaminoglycan (GAG) layer (a protective layer composed of sugars) on the inner surface of the bladder is thought to add to dysfunction of the urothelial layer, and may allow increased permeability of the bladder wall to irritating substances in urine.
Some evidence also suggests immune cell involvement in the pathogenesis of IC/BPS. Extensive infiltration of T- and B-lymphocytes and plasma cells into the bladder mucosa, and the expansion of B-cell populations have been documented. This infiltration appears to be particularly severe in cystitis with Hunner lesions (Maeda et al 2015). It isn’t known whether these cell types are the primary cause of the condition or whether they are infiltrate in reaction to another stimulus.
Changes in protein or hormone expression have been observed, such as urinary nerve growth factor or etio-S (an isomer of testosterone), respectively, and whilst some of these are touted as potential biomarkers for IC/BPS, there is little evidence linking their presence to the pathogenesis of IC/BPS as of yet (Jhang and Kuo 2016).
Since we are unsure what causes IC/BPS, current approaches aim to treat the symptoms. Behavioural therapy is the first port of call, and may include patient education, bladder training, physiotherapy, limiting certain food triggers and stress management approaches (Bo et al 2016). Following on from that are oral, intravesical and intradetrusor therapies, and most of these are off-label use.
Pentosan polysulfate sodium (Elmiron®, Janssen Pharmaceuticals) is an oral drug which is thought to provide relief by replenishing the GAG layer of the bladder. Although it has been approved for use in the US since 1996, it has only recently received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for its use in the EU, and is indicated for “treatment of bladder pain syndrome characterized by either glomerulations or Hunner’s lesions in adults with moderate to severe pain, urgency and frequency of micturition” (CHMP summary opinion for Elmiron 2017). Other off-label oral medications used include amitriptyline, cimetidine and hydroxyzine, and oral pain medication may also be used.
Intravesical therapies are second-line options and include DMSO, heparin or lidocaine. Although this administration route does allow high doses to be delivered directly to the bladder, it comes with the risk of infection and pain from catheterisation. Intradetrusor botulinum toxin A (Botox®) injection has become a more popular option and success rates from its use have elevated it to a third-line treatment option in the American Urological Association guidelines (Jhang and Kuo 2016). Fourth- to sixth-line treatments include further pain management strategies, neuromodulation and surgical options (Jerauld et al 2016).
Part of the legacy of not properly defining IC/BPS is that it is difficult to compare treatments historically, so at least with the new guidelines we can start to properly diagnose the condition and assess different interventions. With advances in our understanding of the biological and psychological aspects of the condition, coupled with a multi-disciplinary approach to treatment, it is hoped that improved treatment of IC/BPS is not too far away.