WIN October 2019

FOCUS 63

Focus on: Crohn’s disease

Mary Nwaezeigwe and Valerie Byrnes discuss the case of a paediatric patient with Crohn’s disease that was resistant to treatment

Dermatological manifestations of Crohn’s disease Having examined the patient’s legs (see Figure 1) a diagnosis of erythema nodosum was made. The typical features of reddish, painful, sometimes multiple nodules seen below the knees, commonly seen at the extensor surfaces, were observed. It rarely requires a histological diagnosis but, if per- formed, the histology reveals a non-specific focal panniculitis. The prevalence of erythema nodosum is higher in Crohn’s disease than in ulcer- ative colitis, and is more common among female patients. 2 The pathogenesis of ery- thema nodosum is not well understood but it could be a type IV hypersensitivity reac- tion. This is usually associated with colitis flares, but not always with severity. Treat- ment in this case is based on controlling the underlying disease. Systemic steroids may be required in severe cases, as well as immunomodulators with azathioprine or biologics with infliximab or adalimumab. Other skin manifestations of Crohn’s dis- ease include: 2 • Pyoderma gangrenosum • Sweet syndrome (ie. acute febrile neutro- philic dermatosis) • Anti-TNF induced skin inflammation such as subcutaneous injection site reaction. The patient was transitioned to the adult services and remained stable on infliximab. Infliximab The patient has been in remission for seven years raising the question of stop- ping infliximab. Long-term prospective data about outcomes following cessation of infliximab in patients with Crohn’s are scarce. In stable patients, the indefinite use of biologic therapy is increasingly being brought up in clinics. Although there are no rules around stopping anti-TNF therapy in Crohn’s, intentional cessation of therapy needs to be made conjointly between the gastroenterologist and the patient. Such decisions should be made on a case-by-case assessment with a frank

A 16-year-old female with Crohn’s dis- ease continued to have clinical symptoms and endoscopic findings consistent with Crohn’s ulceration throughout her colon despite multiple trials with steroids and 6-mercaptopurine. A stricture in the ter- minal ileum was confirmed by a magnetic resonance enterography (MRE). Following this she was commenced on infliximab. A landmark randomised controlled trial (REACH clinical study) 1 demonstrated the efficacy of infliximab for the treatment of paediatric Crohn’s disease. In accord- ance with international guidelines an early top-down approach with biologics ther- apy should be considered in patients with known high-risk factors. These factors are defined as deep colonic ulcerations on endoscopy, persistent severe disease despite adequate induction ther- apy, extensive disease, marked growth retardation, severe osteoporosis, stricturing and penetrating disease, and severe peria- nal disease. As with the adult population, similar risks of opportunistic infections and malignancy can occur. However, it is the occurrence of fatal hepatosplenic T-cell lymphoma that poses a major threat in this patient population. This fatal lymphoma tends to occur in male patients, in 50% of patients aged <20, and in patients who had been treated with long-term thiopurines either alone or in combination with anti-TNF agents. Current international guidelines 1 on the medical management of paediatric Crohn’s states that concomitant azathioprine may be used during the first six months of treatment with infliximab. After six months, stop- ping azathioprine should be considered, especially in boys. The use of low-dose methotrexate can offer an alternative. There have been no case reports of hepatosplenic T-cell lymphoma on inflix- imab alone, therefore this offers a safe treatment option for paediatric patients who need treatment escalation to manage their symptoms.

Figure 1.Before commencing infliximab the patient developed some skin changes

discussion about the benefit-risk ratio at the forefront. 3 Endoscopic, biochemical and clinical remission must be achieved before consid- ering withdrawal of therapy. This is defined as complete endoscopic mucosal healing, normal CRP and a Crohn’s disease activity index of <150. Monitoring the trough levels of TNF and anti-TNF antibodies might play a role in aiding the decision to stop anti-TNF. If the decision is made to stop, it is necessary to monitor CRP and faecal cal- protectin every eight weeks to predict early clinical relapse. This should be followed by an endoscopic exam if these markers are elevated, and recommencement of treat- ment in the event of a relapse. Mary Nwaezeigwe is a gastroenterology registrar and Valerie Byrnes is a consultant gastroenterologist, Galway University Hospital References 1.Kang B,Choe YH.Early biologic treatment in pediatric Crohn’s disease: catching the therapeutic window of opportunity in early disease by treat-to-target.Pediatr Gastroenterol Hepatol Nutr 2018;21(1):1-11 2.Harbord M,Annese V et al for the European Crohn’s and Colitis Organisation [ECCO];The First European evidence- based consensus on extra-intestinal manifestations in inflammatory bowel disease.J Crohn’s Colitis 2016 (Mar); 10(3): 239-54 3.Papamichael K,Vermeire S.Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease. World J Gastroenterol 2015; 21(16): 4773-8A stricture in the terminal ileumwas confirmed by a recent magnetic resonance enterography (MRE).Following this she was commenced on infliximab.

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