Dr. José Carlos Gallego Ojea
Hospitalario Universitario de Ferrol
Perianal Crohn’s Disease (PCD) causes significant morbidity, many times with a serious reduction in a patient’s ability. Fistulising disease comprises the primary, but not the only, manifestation of PCD. Its treatment is difficult, and, unfortunately, requires proctectomy in a considerable percentage of cases, although it only partially solves the patients’ problems.
In inflammatory bowel disease, perianal fistulae are virtually an exclusive manifestation of Crohn’s Disease (CD); although cases have been described in patients with ulcerative colitis, their presence is very uncommon, to such an extent that, for some, it calls the diagnosis into question1.
Fistulising perianal disease may be the first manifestation of CD and precedes confirmation of bowel lesions in up to 30% of the cases2. Furthermore, several studies have proven that its presence is associated with the most severe forms of the disease3.
Contrary to what it may seem, perianal fistulae in CD do not have the same pathogenetic mechanisms as enteric fistulae and, in fact, up to 80% of patients with PCD do not have enteric fistulae4. Therefore, they seem to have different phenotypes and thus is included in the Montreal Classification, in which PCD appears as a differentiated subclassification5. The “cryptoglandular hypothesis”, which assumes that the perianal fistulae may have their origin in the infection of glands located in the Morgagni’s crypts, at the level of the dentate line of the anus, does not seem the most adequate to explain the PCD pathogenesis. Lesions may be the result of the depth of ulcers in the distal rectum or fissures, due to forced exertion during defecation; however, it seems clear that in its etiology, microbiological, immune and genetic factors play a part6.
Imaging methods, particularly magnetic resonance imaging (MRI), provide anatomic and functional information, which at times is difficult to obtain through a solely clinical approximation, especially in patients who have inflammation or abscesses, in which a physical examination is limited.
The introduction of imaging methods that show in detail the anal anatomy, such as MRI and endoanal ultrasound, allow to determine with much more precision than fistulography or computerised tomography (CT) both the extent and complexity of the diseases as well as the presence of abscesses, essential information in order to determine the type of treatment to use. The higher anatomic resolution of these methods also contribute to the success of the surgery by reducing the risk of incontinence or other complications.
From an anatomical viewpoint, the anus, from inside to outside, is made up of:
• An epithelium (not assessable by MRI).
• A layer of smooth muscle that makes up the inner sphincter.
• The intersphincteric space (predominantly occupied by fat and fibres that continue onto the rectal wall).
• An outer layer of striated muscle formed in its lower half by the outer sphincter and, in the upper half, by the puborectal muscle.
On the outside we find the ischioanal fossa, made up of fatty tissue. Fistulae, as we know, are abnormal connections formed by granulation tissue that are established between two epithelial surfaces: in this case, the inner surface of the anal canal (internal orifice) and the skin (external orifice).
It is important to remember that a proper evaluation of the PCD patient includes an endoscopic test to evaluate the luminal disease, specifically the condition of the rectum, a test consisting of local imaging, either with MRI or with ultrasound, and an examination under anaesthesia, in which we can then drain abscesses, place setons, etc., if applicable7. In reference to the imaging test, the MRI is the most objective method. It is more easily comprehensible for other non-radiology specialists and allows for a more precise comparison between the progression tests of each patient. Among the problems with MRI is that it is the most expensive, it can be contraindicated in carriers of pacemakers or other devices, it can be difficult to perform in patients who suffer from claustrophobia and, sometimes, cannot to identify the internal orifice.
The European Consensus 2010 on diagnosing and managing of CD8 affirms in regards to diagnosing PCD:
• Pelvic MRI must be the first method used, because it is accurate and non-aggressive, although it is not needed on a routine basis in simple fistulae (9A).
• Endoanal ultrasound requires experience, but can be used as a supplement to an examination under anaesthesia if rectal stenosis is ruled out. Fistulography is not recommended (9C).
A review performed using evidence-based medicine9 previously showed that MRI is the best method to differentiate simple fistulae from complex fistulae. On the other hand, the only meta-analysis that compares the MRI and the endoanal ultrasound at the time of detecting perianal fistulae concludes that the sensitivity of both methods is similar, although the specificity of the MRI is substantially better10.
MAGNETIC RESONANCE TECHNIQUE
The MRI must be performed in equipment with a field intensity of 1.5 Tesla or higher, although 1 Tesla can be valid, as a result of longer examination times11. In PCD, the use of endocavitary antennae is not recommended since, other than causing discomfort, their field of vision can be insufficient for detecting branching and complications far away from the anus12.
The tests are performed in supine position.
T2-weighted, high-resolution sequences are more useful since they provide adequate contrast between the fistula tracts and affected anatomic structures. Fistulae are usually hyperintense lesions in this type of sequence; it is believed that the degree of intensity can reflect the presence of inflammatory activity (Fig. 1, Fig. 2). It is also impossible to identify cicatricial lesions, typically hypointense, in
• We advise beginning with a sequence in the sagittal plane and performing at least two more planes oriented according to the direction of the anal canal: axial and coronal, taking into account a 45º tilt, approximately. In cases in which 3-D T2-weighted sequences are available, one capture of this type may suffice.
• It is interesting to perform a T2-weighted sequence with fat-suppression techniques, for example in the axial plane, since it enables an easier identification of the inflamed areas and the presence of fluid collections.
• T1-weighted, fat suppression sequences with intravenous gadolinium enable us to clearly distinguish the inflamed tracts and the presence of abscesses; in the former, the granulation tissue occupying the fistula tract is enhanced, while the abscesses and pus remain hypointense. If 3D sequences and programs allowing multiplanar reconstructions are used, it is much more simple to assess the tracts in their entirety (Fig. 3). It is also best to perform this sequence before administering gadolinium, since having the two phases permits application of post-processes such as subtraction, which is the basis of the procedure known as MR fistulography13 (Fig. 4).
• The diffusion image reflects the restriction of free movement of water molecules in tissues that are produced due to the effect of the ischemia, the increase of cellularity or presence of macromolecules. Although they have little spatial resolution, they have a higher contrast with the rest of the tissues, which allows lesions to be identified more easily (Fig. 5). This restriction can be measured, since the image obtained has a quantifiable apparent diffusion coefficient (ADC). Inflamed tissues usually show restricted diffusion, which is why these sequences seem useful for detecting perianal fistulae14. However, as far as its scarce resolution, the diffusion images must be assessed along with the conventional images.
• In perfusion tests (sometimes called DCE-MRI), unlike in conventional tests, in which the post-gadolinium sequence is obtained when the contrast medium has completed its distribution in the tissues, or even has already possibly been eliminated, image acquisition is performed during the passage of the contrast medium through the organ of interest, thus reflecting the dynamic response of this tissue to the arrival of blood and the resulting distribution in the extracellular space. In order to achieve this objective, a compromise between field of vision, spatial resolution and temporal resolution is important. Multi-channel antennae allow for a better signal-noise relation and reduce acquisition times. An analysis of the signal changes that are produced based on time can be carried out from a qualitative, semi-quantitative or quantitative perspective (the latter via software that is less commercially available, for the time being). The most useful semi-quantitative parameters obtained from the analysis of intensity-time curves are the maximum enhancement, the curve’s ascent velocity, maximum value time and the area under the curve.
DESCRIPTION OF THE FINDINGS
Proper identification of the perianal fistulae is a complex process that requires experience on the part of the radiologist15. When describing the findings, a nomenclature known by all professions involved in the management of these patients must be used. Therefore, one of the classifications mentioned below will be used. When describing the fistula tract or fistulae, it is best to refer to its circumferential situation in the anus with location descriptors (anterior-right, posterior-left, etc.) or a clockwise reference (at 4 o’clock, at 11 o’clock, etc.), and to always consider that the view that the radiologist has of the patient is equivalent to the lithotomy position. Although the external orifice of the fistula is easy to identify, the same does not happen with the internal orifice in cases in which it is not placed at the expected level (at the dentate line level).
It is important to describe the relation to the sphincteric complex, the presence of branching, abscesses and, especially, assess its possible extension into the pelvic cavity (over the levator ani muscles) since, when present, non-surgical therapeutic strategies have a high failure rate.
Parks classification16 is the most well-known, since it is a purely anatomic classification. It distinguishes five types of perianal fistulae:
• Intersphincteric fistula. The tract runs from the internal orifice, between both sphincters to the skin. It does not pass through the external sphincter or affect the ischioanal fossa.
• Transsphincteric fistula. From its origin, the tract passes through both sphincters and courses up to the skin through the ischioanal fossa.
• Suprasphincteric fistula. In this case, the tract that runs between both sphincters goes in a cranial direction until surpassing the level of the puborectal muscle. From there it leads to the skin, after passing through the levator ani.
• Extrasphincteric fistula. The tract originates at the rectal level or at the anorectal junction and, without affecting the sphincteric system, courses through the levator ani and the ischioanal fossa to the skin.
• Superficial fistula. Runs from the lower sphincter to the ischioanal fossa and the skin.
The fact that certain additional findings such as the presence of abscesses, branching, etc., which are identifiable via MRI, are not included in the Parks classification, lead to the development of a radiologic classification17, known as the St. James Hospital. This classification establishes five grades:
• Grade 1. Simple linear intersphincteric fistula. The tract runs between the skin and the anal canal, does not show branching and does not surpass the outer sphincter or affect the ischioanal fossa.
• Grade 2. Intersphincteric fistula with abscess or a secondary tract. Although there are complications, the disease never surpasses the outer sphincter. The branching or secondary tract can surpass the mid-line and show contralateral extensions by adopting a “horseshoe” morphology.
• Grade 3. Transsphincteric fistula. The fistula tract passes through both sphincters and goes towards the skin through the ischioanal fossa.
• Grade 4. Transsphincteric fistula with abscesses or a secondary tract in the ischioanal fossa. The tract shows abscessification, generally in the ischioanal fossa, although sometimes also in the intersphincteric region, by adopting an “hourglass” shape.
• Grade 5. Fistulae that extend over the levator ani. Suprasphincteric fistulae run through the intersphincteric space up to the highest point of the levator ani muscle, then passing through it to run to the skin through the ischioanal fossa. The extrasphincteric fistulae originate from a pelvic organ, generally the rectum, and pass through the levator ani heading toward the skin, also through the ischioanal fossa. In any of these two situations, contralateral extensions may appear.
Meanwhile, the American Gastroenterological Association proposes another classification focused on the degree of complexity18: high, intersphincteric and transsphincteric fistulae that pass through the levator ani and those that show branching are the ones considered complex.
Complex fistulae are common in PCD: they show branching or secondary tracts resulting from the ones described above; this branching, when blind, can be complicated and cause abscesses. The most common is the presence of a branching in a cranial direction from the highest point of a transsphincteric tract toward the roof of the ischioanal fossa, and even passing through the levator ani muscle. There may also be branching contralateral to the other ischioanal or “horseshoe” fossa, namely, extensions to both sides from the internal orifice.
Horsthuis et al. proposed a series of five steps to follow for an adequate approach to a pelvic MRI in patients with CD19:
1. Identify each tract and follow it throughout its entire course. If there is more than one, it is very important to look for potential connections between them.
2. Look for abscesses and blind tracts. They are more easily identified in fat-saturated
3. Preferably confirm in the coronal sequence whether the tracts reach or surpass the levator ani muscles.
4. Identify the internal orifice. Usually located at the level of the dentate line, namely, 2 cm from the anocutaneous margin, although it can be located somewhere else.
5. Assess the other secondary findings such as the inflammation of other tissues (proctitis, infiltration, bone oedema) or cancer.
During the assessment, potential errors must be kept in mind such as confusing fistulae with pilonidal sinuses, haemorrhoids or skin tags. Particularly, there is an entity that poses quite a few problems at the time of differential diagnosis, hidradenitis suppurativa. This disease is associated with FPD in CD and
can coexist with it, in a manner that, from a clinical perspective, both clinical as well
as histologic confusion between the two diseases is possible. The coexistence of abscesses in other areas such as groins or armpits and the presence of multiple fistulae and blind tracts without a clear origin in the anorectal area suggest hidradenitis suppurativa7 (Fig. 6 and Fig. 7). The MRI may also suggest hidradenitis suppurativa if thickening of the skin and subcutaneous induration is observed away from the perianal area, inguinal lymphadenopathy and subcutaneous abscesses away from the rectum and anus, with no connection to the pelvic organs20.
This type of fistulae have a few special characteristics. Although they make up 10% of the fistulae in PCD, they cause significant problems consisting of discomfort, infections, dyspareunia, etc. They also show a poor prognosis, since the medical treatment only achieves closure in a low percentage of cases, seton placement does not seem useful and surgical treatment also shows a high rate of recurrences (Fig. 8 and Video 1)21.
This may be the only MRI-based indication for the use of endoanal antennae, as these provide a better view of the tracts due to their lesser extension (between 2 and 2.5 cm) and proximity to the antenna22. However, one cannot forget that other perianal fistulae can exist and that in such cases it will be necessary to also perform a test with conventional antenna.
OTHER POSSIBLE LESIONS IN PERIANAL CROHN’S DISEASE
Fistulae are not the only manifestation of PCD: there are other less known manifestations, most resulting from the primary lesions caused by the disease23. Within this section we can cite:
• Ulcerations: comprising both fissures and the deepest forms that constitute cavitated ulcers (Fig. 9). The latter can trigger serious symptoms and end up causing a fistula tract. They can be confused with Infectious lesions, post-radiation therapy or ulcerated cancers.
• Stenoses: inflammatory stenoses that appear either by anal spasm (type I) or due to authentic fibrocicatricial tissue (type II). They are usually asymptomatic until they reach a high degree.
• Skin tags (Fig. 10): they seem to be caused by lymphoedema due to lymphatic obstruction. They are usually located next to the edge of superficial fissures and are almost always asymptomatic. There are two types: the first comprises large, oedematous and cyanotic skin tags that typically appear next to a healed ulcer; the second, also known as an “elephant ear” flap, is flat, soft and painless. In 30% of cases they contain non-caseating granulomas.
• Neoplastic lesions: although the risk seems rather low, patients with highly progressed perianal disease can develop malignant lesions such as squamous anal carcinoma or adenocarcinoma of the distal rectum. Unfortunately, imaging tests do not help in the early detection of lesions. Although no increased incidence of cancer has been proven in patients with long-standing PCD treated with infliximab, we recommend a meticulous examination and even an anal biopsy under anaesthesia before beginning treatment with this type of drug24.
DETERMINING THE ACTIVITY
From a clinical standpoint, the PCD activity index, or the perianal disease activity index, have been used for a long time. It is based on the assessment of parameters such as secretion, pain, restricted sexual activity, the type of perianal fistula and the degree of induration25.
Another more simple way is the fistula drainage assessment26. Soft compression of the tracts allows us to characterise the fistulae as open or closed. Open fistulae are those from which content comes out, while those from which no content comes out would be called closed, although it is better to classify them as “no drainage”. Using this method, we can classify treated patients as responders when drainage decreases more than 50%, and as being in remission when drainage ceases.
Generally, in a daily clinical routine, it is enough to use these methods based on physical examination. However, if clinical studies are conducted to evaluate the results of a certain treatment, it is mandatory to associate the MRI8.
ROLE OF MAGNETIC RESONANCE
The use of imaging methods, particularly MRI, has proved that the closure of the external orifice is not synonymous with the healing of the fistula, since a detectable lesion often persists in the rest of the tract27. This fact, also shown via ultrasound28, signified an impulse for FPD assessment with imaging methods, not only for surgery planning, but also as a monitoring method for medical or combined treatments.
In 2003, van Assche and Vanbeckevoort developed a numerical severity and extension scale, based on morphological MRI findings29. Their objective in this work was to evaluate the response to infliximab treatment by assessing the number and complexity of the fistulae, the degree of hyperintensity in the T2-weighted sequences, the presence of abscesses and the existence of signs of rectal inflammation. Although this index provides a quick quantitative idea of the complexity and severity of PCD in a patient at a certain time, there is controversy over its usefulness in the follow-up of patients. The same group of authors confirmed that the index shows significant short-term and medium-term drops after treatment, although the same does not occur in longer periods, for example, for a year30. Other studies, which also include long monitoring periods, observed that its value often does not show significant differences between responders and non-responders31 or does not allow to distinguish the patients that have a response from those that only show remission from symptoms32; even in each patient, the value of the index may not show any significant variation after treatment although it may actually show clinical improvement33.
For these reasons, various groups of authors tried to seek other parameters provided by the MRI that give a quantitative idea of the disease and whose variations reflect the effects of the treatments applied. In this way, it was confirmed that patients who present a response or remission show a decrease in hyperintensity in T2-weighted sequences and a reduction of the enhancement after administering intravenous gadolinium, based on subjective estimation32. In reference to post-gadolinium enhancement, it is more accurate to use relative values, namely results from comparisons between the enhanced fistula and the structures that are barely enhanced or not enhanced at all, such as ischioanal fat34.
In regards to the diffusion sequences, they appear to be useful for detecting abscessification in the fistula tract, which is why they can replace the post-gadolinium sequence; the presence of pus shows a significant restriction of the diffusion (Fig. 11), which is why a value of ADC less than 1.1 µm2/s would be indicative of an abscess35. However, in the case of fistulae that have not become complicated with the development of abscesses, in principle it does not appear that the diffusion reflects the degree of inflammatory activity36.
Perfusion tests (DCE-MR) seem to be a little more promising. Tests performed with this type of sequence observe a higher number of pixels that quickly enhance in patients with more a severe disease37. Also semi-quantitative parameters such as maximum enhancement and signal ascent velocity in intensity-time curves show a good correlation with the PDAI. On the other hand, a quantitative parameter, namely the volume transfer constant or ktrans, can be indicative of response to anti-TNF drug treatment38.
Another interesting aspect is to be able to determine when is the right time to perform the imaging test in patients who are receiving medical treatment. It has been already mentioned that there is usually a quick clinical response, although it is not accompanied with the disappearance of the MRI findings. Several studies prove that changes occur in the first weeks as a result of the treatment, which leads to lower index scores. However, the MRI tests performed in the medium term (26–52 weeks) confirm that this improvement is maintained or even increases in responding patients30. Similarly, another test showed that patients who were in remission at six months remained so a year afterwards, even if they had discontinued the treatment31. However, MRIs that are performed at a longer period (over a year) usually show another increase in activity or in the index score and do not allow to differentiate between responders and non-responders.
Thus, it seems right to propose a baseline pelvic MRI test before beginning treatment, and another at six months to confirm response, if any (Fig. 12). The disappearance or significant decrease in findings in this second MRI would have a prognostic value over the long-term progression, which helps to also determine the continuity of the treatment.
• The initial test for PCD patients must include an imaging method. Selecting between a MRI or an endoanal ultrasound will depend on the availability of each site, the accumulated experience, etc., although the actual evidence and international recommendations have a slight preference for MRI.
• The MRI must be performed with a multi-channel external antenna, preferably by radiologists with experience.
• The report must describe the fistula tract in relation to the anatomic structures of the anus in an attempt to identify the internal orifice, and the presence of abscess, branching or other complications. It would be interesting to also include an index that quantifies the severity of the disease. One must not forget that there are other perianal manifestations of CD that must also be assessed, nor is it possible to confuse the fistulae with other disease processes.
• When clinical studies on the response to certain treatments, such as anti-TNF drugs, are proposed, the performance of MRI is mandatory. Other than the baseline test, an MRI must be repeated at 6 months, given the capacity it has at that time to assess the response and establish a prognosis.
• In conclusion, it is important that all involved in managing this type of patient use the same nomenclature, classification, etc. Therefore it is ideal for the site to have a multidisciplinary team for this purpose and that a radiologist specialising in this type of pathology be part of this team.
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