A 32-year-old Caucasian woman with a 12 pack-year history of smoking presents with diarrhea and right, lower quadrant colicky pain. You note tender, red nodules on her legs. On radiological examination, this is the presentation of the patient, what is the most likely diagnosis?

Ans. (b) Crohn's disease. The image represents cobblestone appearance which is characteristic of Crohn's disease. Differences between ulcerative colitis and Crohn's disease * UC is a mucosal disease, whereas CD affects the full thickness of the bowel wall * UC produces confluent disease in the colon and rectum, whereas CD is characterized by skip lesions * Ulcerative colitis affects the colon; Crohn's disease can affect any part of the gastrointestinal tract, but particularly the small and large bowel * CD more commonly causes stricturing and fistulation * CD is often associated with perianal disease, whereas this is unusual in UC * CD affecting the terminal ileum may produce symptoms mimicking appendicitis, but this does not occur in UC * Resection of the colon and rectum cures the patient with UC, whereas recurrence is common after resection in CD * Granulomas may be found on histology in CD, but not in UC Image source- Ref of below image- Ref- Crohn disease, also known as regional enteritis, is an idiopathic inflammatory bowel disease characterised by widespread discontinuous gastrointestinal tract inflammation. The terminal ileum and proximal colon are most often affected. Extraintestinal disease is common. Epidemiology The diagnosis is typically made between the ages of 15 and 25 years with no gender predilection 5. There is a familial component and incidence varies geographically. Clinical presentation Patients typically present with chronic diarrhoea and recurrent abdominal pain, although occasionally the presentation is with a complication or an extraintestinal manifestation. Anaemia may be present and C-reactive protein may be elevated 29. Faecal calprotectin has been increasingly used in recent years to: distinguish inflammatory bowel disease from irritable bowel syndrome assess disease activity in inflammatory bowel disease, including acute exacerbations and response to treatment 26 Pathology Crohn disease remains idiopathic, although infective agents have been gaining in popularity as a possible cause, including the measles virus and atypical mycobacterium. As there are definite genetic factors at play, multiple factors are likely to contribute 1. Incidence is higher in people with first degree relatives having IBD, reaching up to 10%. Also, there has been shown 30-50% chance of developing the disease in mono- or heterozygous twins. Initially, the disease is limited to the mucosa with neutrophilic cryptitis and lymphoid hyperplasia, lymphoedema and shallow aphthoid ulceration. As the disease progresses, the entire bowel wall becomes involved, with linear longitudinal and circumferential ulcers extending deep into the bowel wall, predisposing to fistulae. Inflammation also extends into the mesentery and over time leads to chronic fibrotic change, and stricture formation 5. Anywhere along the digestive tract, including mouth and oesophagus mucogingivitis, mucosal tags, deep ulceration, cobblestoning, lip swelling and pyostomatitis vegetans, oesophageal ulcers and strictures Extraintestinal manifestations include 3,15-17: skin erythema nodosum pyoderma gangrenosum joints arthritis seronegative spondyloarthritis sacroiliitis (one of the most frequent extraintestinal manifestations) eyes episcleritis iritis uveitis (acute anterior uveitis) liver and biliary system pericholangitis primary sclerosing cholangitis (PSC) (more common in ulcerative colitis) autoimmune hepatitis cirrhosis gallstones: seen in 30-50% 8 hepatic abscess 8 pancreatitis renal tract renal calculi containing oxalate. The poor fat absorption results in binding of calcium by fats, which in turn reduces the amount of calcium that can bind to oxalate, therefore increasing the amount of unbound oxalate available for resorption; this resorption occurs in the colon, and therefore patients with an ileostomy do not have the same increased risk pulmonary and thoracic associations bronchiectasis, mosaic perfusion, and air trapping chronic bronchitis, interstitial lung disease, cryptogenic organising pneumonia, necrobiotic nodules 30 Radiographic features The characteristic of Crohn disease is the presence of skip lesions and presence of discrete ulcers. The frequency with which various parts of the gastrointestinal tract are affected varies widely 5: small bowel: 70-80% 5,6 small and large bowel: 50% large bowel only: 15-20% The choice of investigation modality depends on local expertise and availability. CT and MR enteroclysis are similar in sensitivity for active inflammation (89% vs 83% respectively) and both are somewhat better than small bowel follow-through (67-72%) 6. The lack of ionising radiation from MRI would make it a better option, however, the availability of MRI is limited in many countries. Ultrasound is also an option for diagnosing active disease, follow-up and assessing complications 20. Reported sensitivity 75-94% and specificity 67-100% 20. Fluoroscopy Features on barium small bowel follow-through include: mucosal ulcers aphthous ulcers initially deep ulcers (>3 mm depth) longitudinal fissures transverse stripes when severe leads to cobblestone appearance may lead to sinus tracts and fistulae widely separated loops of bowel due to fibrofatty proliferation (creeping fat) 2 thickened folds due to oedema pseudodiverticula formation: due to contraction at the site of ulcer with ballooning of the opposite site string sign: tubular narrowing due to spasm or stricture depending on the chronicity partial obstruction on control films presence of gallstones, renal oxalate stones, and sacroiliac joint or lumbosacral spine changes should be sought Ultrasound Ultrasound has a limited role, but due to it being cheap and available and not involving ionising radiation, it has been evaluated as an initial screening tool for active disease and also for follow-up and to assess complications 4,20. Typically examination is limited to the small bowel and wall thickness assessed: bowel wall thickness should be <3 mm The usefulness of this finding needs to be interpreted in the context of pretest probability (i.e. thickness of less than 3 mm helps exclude the disease in a low-risk patient, and a thickness of greater than 4 mm helps establish the diagnosis in a high-risk patient) 4. As it has difficulty examining the whole bowel, it is not appropriate as a true diagnostic test. On Doppler evaluation, increased superior mesenteric artery (SMA) flow volume and decreased SMA resistive index (SMA RI) also correlate with disease activity. Successful treatment may result in the normalisation of these imaging parameters 12. Other features on ultrasound 20: non-compressible, rigid, fixed bowel wall perienteric fluid creeping fat - echogenic area (representing proliferation of adipose tissue that extends around active inflammation) separating bowel loops gut signature - lost or preserved strictures - fibrotic (maintains gut signature) or inflammatory (loss of gut signature) abscess fistula Ultrasound does, of course, have a significant role to play in the assessment of: perianal disease: rectal ultrasound, endoanal ultrasound hepatobiliary disease CT CT examination can be carried out with both intravenous and intraluminal contrast (positive or negative) 5: fat halo sign comb sign bowel wall enhancement bowel wall thickening (1-2 cm) which is most frequently seen in the terminal ileum (present in up to 83% of patients) 8 strictures and fistulae mesenteric/intra-abdominal abscess or phlegmon formation 8 abscesses are eventually seen in 15-20% of patients 8 CT is also able to give valuable information on: perianal disease hepatobiliary disease MRI MRI enterography has no ionising radiation and an ability to evaluate both mural and extramural involvement. It has become an increasingly important part of the management of patients with Crohn disease. MRI enteroclysis may be attempted in select patients. MR enterography MR enterography can be a useful technique for evaluation of the bowel. Inflamed loops of bowel demonstrate thickening >3 mm and increased mural contrast enhancement 22. Increased T2W signal in the thickened bowel wall is particularly helpful in evaluating for acute inflammation 25. Extramural disease is where MRI excels: fibrofatty proliferation thickening of extramural fat, which separates bowel loops equivalent to the fat halo sign on CT vascular engorgement: comb sign stenoses and strictures Coronal cine sequences (bSSFP) can also be useful in diagnosis. Inflamed loops of bowel frequently demonstrate decreased peristalsis. MRI enteroclysis MRI enteroclysis requires the placement of a nasojejunal catheter through which 1.5-2 L of contrast solution (e.g. water with polyethylene glycol and electrolytes) are injected 2. Spatial resolution is not as good as with conventional fluoroscopic enteroclysis, and thus minor mucosal changes are not apparent. When the disease is transmural, with cobblestone appearance, the abnormalities are evident as high T2 signal linear regions, provided adequate distension is achieved 2. Standard MRI Standard MRI can also give valuable information: perianal disease hepatobiliary disease sacroiliac joints, spine and large joints Treatment and prognosis Management is complex as the condition is chronic with a relapsing-remitting course. Medical management includes corticosteroids, 5-ASA preparations, immunomodulation (e.g. azathioprine, cyclosporine, methotrexate) 7. Surgical management is reserved for complications including: strictures adhesions and bowel obstructions fistulae perianal disease perianal fistula perianal abscess History and etymology It is named after Burrill Bernard Crohn (1884-1983), an American gastroenterologist, who described the condition as 'regional ileitis' in his seminal 1932 paper 11,24. However, the first definite description (but see below) was nearly twenty years prior, by Sir T (Thomas) Kennedy Dalziel (1861-1924), a Scottish surgeon, in 1913 21,23. Antoni Lesniowski (1867-1940), a Polish surgeon, described a small bowel condition in 1904 in a small series of four patients, with similarities to Crohn disease, although it remains controversial if it was actually Crohn's 27,28. At least one of the patients probably actually had ileal tuberculosis. Nevertheless Polish physicians and journals usually call the condition Lesniowski-Crohn disease. Differential diagnosis The differential diagnosis depends on the presenting symptom. When terminal ileitis is the main presentation, then differentials (adjusted for patient's age) include 1: acute appendicitis Yersinia ileitis mesenteric adenitis ileocaecal tuberculosis 9 malignancy When colonic involvement is the predominant feature then other considerations include: ulcerative colitis acute diverticulitis acute epiploic appendagitis ischaemic colitis pseudomembranous colitis infectious colitis