The term ‘interstitial cystitis’ has been replaced by BPS introducing a new nomenclature, based on diagnostic and classification criteria [1, 2].

The etiology of IC/BPS is poorly understood, and its pathogenesis may involve multiple pathways leading to a common clinical entity [3].

Frequency, urgency and pain on bladder filling are the most common symptoms of BPS. All urodynamic volumes are reduced. Associated conditions include psychological distress, depression, history of sexual assault, irritable bowel syndrome and fibromyalgia. Cystoscopy remains the test for definitive diagnosis, with visualization of hemorrhage on cystoreduction. A multidisciplinary treatment approach is essential in the management of this condition [4]. An association between anxiety disorder (AD) and IC/BPS has been shown. Clinicians should evaluate and monitor the presence of IC/BPS in patients with AD [5]. Sexual dysfunction was an important component of IC/BPS phenotype, and adding a sexual dysfunction domain to the UPOINT system improved the association with IC/BPS symptom severity [6].

No structural ANS abnormalities in IC/BPS subjects have been shown. Higher baseline heart rate (HR) supports the concept of functional rather than structural change in the ANS, such as abnormality of sympathetic/parasympathetic balance that will require further evaluation [7]. Altered sensory processing in patients with IC/BPS may result from a deficiency of the central nervous system to adequately filter incoming visceral afferent information [8]. White matter abnormalities closely correlated with symptoms of IC/BPS, including bladder pain and urinary symptoms. These anatomical brain alterations suggest that there are neuropathological contributions to chronic urological pelvic pain [9]. Changes in somatosensory gray matter may have an important role in pain sensitivity as well as affective and sensory aspects of interstitial cystitis [10]. Women with IC/BPS have a sensorimotor component to the pathological condition involving an alteration in intrinsic oscillations and connectivity in a cortico-cerebellar network previously associated with bladder function [11].

The classic type of interstitial cystitis with Hunner’s lesions, bladder pain syndrome type 3C according to current terminology, stands out as a well-defined phenotype; it has to be evaluated separately in clinical studies and practice, as treatment requirements differ importantly between this and other phenotypes [12].

Publications did not indicate specific questionnaires able to show symptom differences between type 3C and non-type 3C BPS. Literature presents no questionnaires able to differentiate subtypes of BPS (e.g. type 3C and non-type 3C BPS). We suggest using the ESSIC guideline to differentiate between subgroups in BPS [13, 14].

A thorough clinical assessment including a ‘four step protocol’ for investigation of CPPS has been proposed, aiming to obtain supplementary information to refine the therapeutic management. The ‘four step protocol’ involves: (step 1) a careful history with questioning for complaints in other systems. The evaluation of previous assessments and reports (step 2). Step 3 involves an extensive clinical assessment (e.g. neurological, hernia’s (e.g. inguinal, Spighelian), an assessment the external sex organs and the small pelvis via rectal and vaginal ways). The extensive clinical assessment of the musculoskeletal system (step 4) includes an assessment of the full spine and pelvic girdle. Muscular pain, tendons and pain points have to be determined. Attention for emotional consequences as a result of the chronic suffering is important assessing patients with CPPS [14–17].

Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for IC/BPS, and could be a tool for the differential diagnosis of IC/BPS and other sensory bladder disorders [18]. Urodynamic tests, cystoscopy and hydrodistension, biopsies and pathologic evaluation are in the process of finding a place in the diagnostic tree [19]. Correlations between cystoscopic findings, maximal bladder capacity and bladder histology were found [20]. Over active bladder (OAB) and IC/BPS are different symptoms complexes that share urgency as a common symptom. None of them have a specific symptom although pain on bladder filling is the hallmark symptom in IC/BPS [21]. There is considerable overlap of self-reported symptoms between IC/BPS and OAB. This overlap raises the possibility that the two conditions represent a continuum of a bladder hypersensitivity syndrome [22].

Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for IC/BPS, and could be a tool for the differential diagnosis of IC/BPS and other sensory bladder disorders [18, 23, 24]. Urinary nerve growth factor (NGF) but not prostaglandin E2 increases in patients with IC/BPS and detrusor overactivity [25]. There is an increased level of NGF in the IC/BPS patients [26].

One of the most common findings in IC bladders is denudation or thinning of the bladder epithelium, suggesting an altered regulation of urothelial homeostasis [27]. Glomerulations should be included in the diagnosis or phenotyping of IC/BPS. Glomerulations do not correlate with symptoms and are found in patients without IC/BPS [28]. Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow the differentiation of IC/BPS and overactive bladder syndrome, even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligo−/a-symptomatic cases, and may permit timely treatment to prevent disease progress [29].

Mast cell counting should be done in a standardized way and the pathology report should include several data as proposed before [19]. Twenty seven mast cells/mm² is considered indicative of mastocytosis [30]. Mast cell density does not appear to correlate with duration of symptom amelioration after complete transurethral resection of Hunner’s lesions [31]. Subepithelial mast cell distribution was characteristic of IC/BPS with Hunner lesions. Detrusor mastocytosis had poor predictive value for IC/BPS. Mast cell assessment did not distinguish IC/BPS without Hunner lesions from overactive bladder syndrome [32].