Challenges in the management of IBD

Medical management of IBD is not without its share of challenges.While a detailed discussion on each one of them is outside the scope of this article,an introductory survey is presented with the view of providing a holistic overview.

Diagnosis

While it is clear that IBD comprises two distinct and heterogenous clinical diseases,namely Ulcerative Colitis & Crohn's Disease,the allocation of a patient to either group is entirely dependent on the clinical manifestation, in the absence of which there remains only the subjectivity of clinical impression.Consequently,a significant proportion of patients cannot be classified in one or the other category and have to be classified into a third category referred to as IBD-Unclassified (IBDU). This stems from an absence of a single or multiple gold standard test/s that can enable an unequivocal diagnosis.

Another challenge that surfaces from this diagnostic lacunae is the inability to have a screening protocol which could enable early diagnosis,especially in CD since early detection and treatment could go a long way in preventing long-term complications such as strictures and fistulae,thereby reducing the burden on the health infrastructure as well as saving the patient from an avoidable financial burden as well as the morbidity associated with such conditions.

The solution lies in discovery and standardization of an appropriate test or tests.Work is on-going in the field of serology, radiologic imaging, endoscopy and fecal markers of inflammation and it is anticipated that an appropriate protocol for diagnosis and screening will surface.A list of putative candidates is shown in the figure below:

Hazards of Therapy

LYMPHOMAS

There is growing concern about the risk of increased occurrence of cancer. Generally, the chronic deployment of immunosuppressive therapy in various conditions can increase the risk of malignancies due to the suppression of immune mechanisms that are responsible for screening and effectively dealing with cancer cells. Besides the suppression of immune responses, the drugs per se can have the potential of triggering the cancerous process. Thus, regular suitable screening of patients who are on medical therapy for IBD should be recommended.

The malignancy of particular concern is non-Hodgkin's lymphoma, and varying degrees of higher than normal incidences have been reported with the various immunosuppressive agents (Methotrexate, etc.) as well as anti-TNF-alpha agents (Infliximab, etc.)

Infections:

Corticosteroids, which are mainstay of IBD management, are also known to suppress immunity and predispose to infections. In addition, while step-up therapy regime has been the recommended way to go in the past, there is an emerging view of thought that a top-down regime might be more beneficial for the patient. Thus, deployment of immunomodulators (AZA, 6-MP & Methotrexate) and biological agents is being contemplated at an earlier stage of the disease management. This, obviously, increases the duration for which the patient is exposed to such suppressive therapies. And, as a result, the patient can find oneself at a greater risk of getting infected by an infection that one would normally not have contracted.

Infections with opportunistic microorganisms can also increase. Viral infection and fungal infections that would normally not have caused any disease can lead to debilitating infective states. Moreover, latent infections, such as tuberculosis, deep fungal infections., herpes infections) can also undergo resurgence. Thus, prevention of infections, and their treatment when necessary, emerges as a major challenge in the chronic management of IBD.

STEROID DEPENDENCY

Typically, steroids are used in induce remission in IBD. While the response is satisfactory, subsequent attempts to taper off steroids fails with aggravation of the disease. Such patients are considered to be steroid-dependent. They pose a special challenge due to the numerous hazards of chronic steroid therapy. Thus, other appropriate immunomodulating drugs need to be co-prescribed. This choice is often unsuccessful.

PROGNOSIS and RESPONSE TO THERAPY

Management of a chronic disease that is replete with remissions and recurrences necessitates intermittent evaluation of response to therapy to permit optimization of therapy by tweaking the treatment or changing it, as the situation may warrant. In routine practice, clinical symptoms in the form of stool characteristics (frequency and presence of blood) and constitutional symptoms have been the main-stay of assessment. Adequate as this might be in some cases, it is far from fool-proof. Symptom-based activity indices have been formulated but there deployment in routine clinical practice is not universal. Moreover, medicine-related side-effects can often confound the clinical assessment. Appearance of irritable bowel syndrome can also complicate the symptomatic assessment.

Thus, there is need for more objective and definitive criteria for assessing not only the response to therapy but the level of disease activity as well as the progression of the same. With that objective, assistance of non-specific investigations such as ESR and CRP has been sought. Recording of "mucosal lesion healing" by endoscopy is another option that has surfaced with advancement in technology. However, the correlation between mucosal lesion healing and symptomatic progression is often not entire. Therefore, there is need for a identification and validation of one or more suitable criteria and the promulgation of appropriate guidelines for assessing the response to therapy.

Extra-Intestinal Manifestation

Various epidemiological and other studies have amply illustrated the existence of extra-intestinal manifestations and have pegged the incidence to between 6% and 45%.Active and conscious screening will certainly yield higher incidences. The common extra-intestinal manifestations are:

  1. Ankylosing spondylitis (AS) can occur in the axial form (vertebrae and/or sacroiliac) or the appendicular form (involvement of the peripheral joints).The latter can respond to treatment of IBD but the former does not. Thus,NSAIDs and other anti-inflammatory agents have to be used.These,in turn,can adversely affect the IBD. Thus, concomitant AS can pose a problem in the overall management of the patient.
  2. Other spondyloarthropathies, if present,pose similar challenges as AS (inflammatory condition affecting the joint-related soft-tissues such as tendon,synovial membrane and ligaments).
  3. Episcleritis (inflammation of sclera),Uveitis (inflammation of iris)
  4. Osteoporosis due to nutritional deficiency and/or chronic steroid administration
  5. Skin manifestations (erythema nodosum,pyoderma gangrenosum)
  6. Aphthous ulcerations (ulcers in the mouth)