Ulcerative Colitis and Atopic Dermatitis
Ulcerative colitis is a chronic form of intestinal inflammatory disease that affects the colon (large intestine). Most commonly, adults are first affected aged 30–40 years. It causes ulcers on the colon’s lining and can result in disability and a lower quality of life. Characterised by relapsing and remitting mucosal inflammation, it starts in the rectum and extends to other parts of the colon.
To describe it more medically, ulcerative colitis is associated with damage to the mucosal barrier, allowing the luminal microflora to trigger a sustained and uninhibited inflammatory response. Among the inflammatory cells, T helper cells perpetuate enterocyte apoptosis and inhibit mucosal healing. IL-13, produced by NK T cells, also contributes to epithelial injury. Additionally, innate lymphoid cells, homeostatic at steady state, contribute to the cytokine production, perpetuating inflammation. Mucosal injury and damage is also associated with dysbiosis, which is thought to contribute to the inflammatory cascade.
An increased understanding of the mucosal immune system has led to an expanding array of therapies. The aim of therapy is to induce and maintain clinical and endoscopic remission. Aminosalicylates are the main choice of treatment for a mild to moderate form of the disease, topical and systemic steroids can be used to treat ulcerative colitis flares, while immunosuppressants and biological drugs are used in moderate to severe disease. Colectomy is needed in up to 15% of patients. The annual direct and indirect costs related to ulcerative colitis are estimated to be as high as €12.5–29.1 billion in Europe and US$8.1–14.9 billion in the USA.
However, the number of drugs modulating different disease pathways is expected to expand in the near future. There are at least 27 new drugs for ulcerative colitis with either recently completed or active trials. Nevertheless, the optimum level of symptom control and remission that is needed to prevent long-term complications remains to be fully understood.
Atopic dermatitis is the most common chronic skin disorder worldwide. It often causes a red, itchy rash, mostly on the cheeks, arms and legs. While the condition may occur at any age, it typically starts in childhood, with changing severity over the years. The cause is unknown but believed to involve genetics, immune system dysfunction, environmental exposures, and impairment of the permeability of the skin. Up to one third of patients suffer from other atopic diseases such as food allergy, rhinitis and asthma. Rheumatoid arthritis, cardio-metabolic traits, psychiatric conditions and inflammatory bowel disease are also associated with atopic dermatitis.
The disease is based on a strong genetic component and triggered by environmental factors. Multiple risk loci have been identified by gene mapping studies, some of which overlap with other immune-mediated diseases and are shared by both diseases. Atopic dermatitis is characterised by epidermal barrier deficiency along with excessive T-cell activation of differing polarity, with a strong Th2 and Th22 component, but appears to be more heterogeneous, involving multiple immune pathways with different features. However, with a few notable exceptions, the causal genes and their molecular mechanisms have not been identified so far.
Due to its high prevalence, the associated medical costs are comparable to those of asthma and the significant negative impact on the patients’ quality of life is similar to diabetes.