Common Disease-Modifying Agents and Their Targets

Disease-modifying agents (DMARDs) are a group of drugs used to treat various diseases, including rheumatic disease, gastrointestinal disease, and neurological conditions. These agents have different targets in the immune system, and some of the most common ones are discussed below.

Antibody against Tumour Necrosis Factor-alpha (TNF-α)
TNF-α inhibitors, such as infliximab and adalimumab, are used to treat rheumatic disease and inflammatory bowel disease. These agents increase susceptibility to infection and should not be administered with live vaccines.

Antibody against CD20
Rituximab is a monoclonal antibody against CD20 and is used to treat aggressive non-Hodgkin’s lymphoma.

Interleukin (IL)-1 Blocker
Anakinra is an IL-1 receptor antagonist used to treat rheumatoid arthritis.

α-4 Integrin Antagonist
Natalizumab is a humanised monoclonal antibody against α-4-integrin and is used to treat multiple sclerosis.

IL-2 Blocker
Daclizumab is a monoclonal antibody that binds to the IL-2 receptor and is used to prevent acute rejection following renal transplantation.

Targets of Disease-Modifying Agents

Modes of Transmission for Hepatitis A, B, and C

Hepatitis is a common cause of jaundice and should be considered in patients with abnormal liver function tests. The clinical features of acute hepatitis include a non-specific prodromal illness followed by jaundice. Hepatitis A and E are highly infectious and spread through the faeco-oral route. Infected individuals excrete the virus in their faeces for up to 5 weeks. Infection is more common in areas of poor sanitation. Hepatitis B and C can be spread through vertical transmission, sexual contact, blood products, and saliva. It is important to ask patients with jaundice if they had any blood products prior to 1991, as blood products in the UK have been screened for hepatitis C since then.

Investigations for Suspected Inflammatory Bowel Disease

Suspected cases of inflammatory bowel disease (IBD) require a thorough assessment to determine the underlying cause. A plain abdominal film is essential in the initial evaluation to exclude colon dilation and assess the extent of disease. Sigmoidoscopy is recommended for all patients presenting with diarrhea, as it allows for the visualization of the sigmoid colon and rectal biopsies for histology. Colonoscopy may be preferred in mild to moderate disease, while CT scans are helpful in evaluating disease activity and complications. An erect chest X-ray is important if a pneumoperitoneum is suspected. However, in the absence of peritonism or upper gastrointestinal pathology, the abdominal film is the most appropriate next investigation to exclude a toxic megacolon.

Common Abdominal Exam Findings and Their Significance

Abdominal exams are an important part of diagnosing various medical conditions. Here are some common findings and their significance:

Tenderness over McBurney’s point: This is a sign of possible appendicitis. McBurney’s point is located a third of the way from the right anterior superior iliac spine to the umbilicus.

Grey–Turner’s sign: Flank bruising is a sign of retroperitoneal hemorrhage, which is commonly associated with acute pancreatitis.

Murphy’s sign: This suggests cholecystitis. The examiner places their hand below the right costal margin and the tender gallbladder moves inferiorly on inhalation, causing the patient to catch their breath.

Tinkling bowel sounds: High-pitched, ‘tinkling’ bowel sounds are typically associated with mechanical bowel obstruction.

Absent bowel sounds: This is suggestive of paralytic ileus, which most commonly occurs after abdominal surgery.

Choosing the Best Investigation: A Case Study

In this case study, a patient presents with non-alcoholic fatty liver disease (NAFLD), raised ALT, impaired glucose regulation, acanthosis nigricans, and a high BMI. The question is, what investigation should be done next?

Ultrasound liver is the best investigation in this case. It is quick, inexpensive, and can provide enough information to guide management at initial stages. Weight management and dietary modification can help abate symptoms.

Screening for hereditary haemochromatosis is not appropriate in this case, as the patient does not complain of arthritis, diabetes, or changes to the skin.

Haematinics are not necessary, as the Hb is normal.

A CT scan of the abdomen would be useful, but it is costly and would result in the patient receiving radiation. It should not be the next best investigation.

Serum ceruloplasmin is not necessary, as there is nothing in the history to suggest Wilson’s disease.

In conclusion, choosing the best investigation requires careful consideration of the patient’s history and symptoms. In this case, ultrasound liver is the most appropriate next step.

Serologic Markers of Autoimmune Diseases

There are several serologic markers used to diagnose autoimmune diseases. These markers include perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), anti-dsDNA antibody, antinuclear antibodies (ANA), anti-smooth muscle antibody (ASMA), and anti-Saccharomyces cerevisiae antibody (ASCA).

p-ANCA is elevated in patients with ulcerative colitis and/or primary sclerosing cholangitis (PSC). Anti-dsDNA antibody is found in systemic lupus erythematosus (SLE). ANA is a sensitive, but not specific, marker for a variety of autoimmune diseases such as SLE, mixed connective tissue disorder (MCTD), and rheumatoid arthritis (RA). ASMA, ANA, and anti-liver–kidney microsomal antibody-1 (LKM-1) are serologic markers of autoimmune hepatitis. Increased levels of ASCA are often associated with Crohn’s disease.

These serologic markers are useful in diagnosing autoimmune diseases, but they are not always specific to a particular disease. Therefore, they should be used in conjunction with other diagnostic tests and clinical evaluation.

The patient is suspected to have acute cholecystitis, and a confirmation of the diagnosis will rely on an ultrasound scan of the abdomen. To manage the patient’s symptoms and prevent sepsis, it is essential to administer intravenous antibiotics and fluids. Antiemetics may also be necessary to prevent dehydration from vomiting. It is recommended to keep the patient ‘nil by mouth’ until the scan is performed and consider prescribing analgesia for pain relief. An NG tube is not necessary at this stage, and an OGD or ERCP may be appropriate depending on the scan results. The NICE guidelines recommend cholecystectomy within a week of diagnosis.

Understanding the Lifetime Risk of Colorectal Cancer in Hereditary Syndromes

Hereditary syndromes such as HNPCC and FAP are associated with an increased risk of developing colorectal cancer. HNPCC syndrome has a lifetime risk of approximately 50-70% for colorectal cancer, as well as an increased risk for endometrial and ovarian cancer. Screening is recommended from age 25 and should include annual colonoscopy and other tests for women. FAP, on the other hand, has a 100% lifetime risk for colorectal cancer. Underestimating the lifetime risk for HNPCC syndrome can be dangerous, as it may lead to delayed or inadequate screening. It is important to understand the risks associated with these hereditary syndromes and to follow recommended screening guidelines.

Imaging Modalities for Abdominal Conditions: Choosing the Right Test

When a patient presents with abdominal symptoms, choosing the appropriate imaging modality is crucial for accurate diagnosis and timely treatment. Here are some considerations for different tests:

Abdominal X-ray: This is a quick and effective way to assess for conditions such as toxic megacolon, which can be life-threatening. A dilated transverse colon (>6 cm) on an abdominal X-ray is diagnostic of toxic megacolon.

Abdominal ultrasound: This test is useful for assessing the abdominal aorta for aneurysms, but it is not recommended for suspected inflammatory bowel disease.

Oesophagogastroduodenoscopy (OGD): This test is recommended for patients with suspected oesophageal or gastric pathology, but it is not useful for assessing the large colon.

Colonoscopy: While colonoscopy is a valuable tool for diagnosing ulcerative colitis, it is contraindicated during acute flares as it increases the risk of bowel perforation.

Computed tomography (CT) scan of the kidney, ureters and bladder: This test is indicated for patients with suspected kidney stones, which typically present with loin to groin pain and haematuria.

In summary, choosing the right imaging modality depends on the suspected condition and the patient’s symptoms. A prompt and accurate diagnosis can lead to better outcomes for patients.

Common Causes of Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding can be caused by various conditions. Here are some of the most common causes:

Mallory-Weiss Tear
This tear in the mucosa is usually caused by repeated vomiting, resulting in increased abdominal pressure. Young patients with a clear history may not require further investigation, and bleeding usually resolves without treatment.

Oesophageal Varices
This condition should be considered in patients with signs of chronic liver disease or a history of heavy alcohol intake. Oesophageal varices can be life-threatening, with mortality rates as high as 30%.

Peptic Ulceration
Peptic ulceration is a common cause of upper gastrointestinal bleeding, especially in patients who use non-steroidal anti-inflammatory drugs (NSAIDs), smoke, or have Helicobacter pylori infection. Patients with peptic ulcer disease should be tested for H. pylori and treated accordingly.

Reflux Oesophagitis
This condition is characterized by heartburn and can be asymptomatic. It is usually an incidental finding on endoscopy and can be treated with antacid medication.

Haemophilia
Haemophilia is a condition that increases the risk of bleeding due to the absence of clotting factors. While spontaneous gastrointestinal bleeding is rare, patients may present with spontaneous bleeding in other parts of the body, such as joints.