A 45-year-old Caucasian man is referred for further workup of chronic abdominal pain and diarrhea. These symptoms have been present for 2 months, and he has lost 10 kg of weight over this time. He also reports that he has developed pain in multiple joints that comes and goes and seems to spread from one joint to the next. He denies fevers, chills, chest pain, shortness of breath, vomiting, episodes of constipation, or hematochezia. He is married and works as a farmer, with no recent sick contacts or travel. His vitals are within normal limits, and his examination is unremarkable. A complete laboratory workup is unremarkable. He undergoes a colonoscopy, which is normal, and then undergoes an upper endoscopy. Biopsy of the small intestine shows many macrophages within the lamina propria that stain positive with periodic acid-Schiff (PAS).
Which of the following is likely to cure this patient of his chronic diarrhea?
Antibiotics. Chronic diarrhea is defined as a decrease in stool consistency that lasts longer than 4 weeks. There are many causes of chronic diarrhea, and the diagnosis often requires an extensive workup. Important diagnostic categories to consider are infections, osmotic diarrhea (with an increased stool osmotic gap, such as lactose intolerance), secretory diarrhea (e.g., hormones, laxative abuse), chronic inflammation (e.g., inflammatory bowel disease, ischemic colitis), functional diarrhea (decreased motility, such as irritable bowel syndrome), and malabsorption (e.g., pancreatic disease, celiac disease).
This patient has Whipple disease, a rare cause of chronic diarrhea that is due to infection with Tropheryma whipplei. Though this bacterial species can infect a wide variety of patients, the majority are middle-aged Caucasians, with a large percentage being farmers (or at least having exposure to soil or animals). Four features that suggest the diagnosis are chronic diarrhea, abdominal pain, weight loss, and migratory arthralgias; however, the disease may present without any GI symptoms and can alternatively present with CNS disease or endocarditis. The diagnosis is confirmed with biopsy showing an abundance of macrophages in the lamina propria with intracellular material that stains positive with PAS.
(A) Radioiodine would be an appropriate treatment for hyperthyroidism, which can also cause weight loss and diarrhea but is unlikely to cause migratory arthralgias. (B) Dietary changes would cure conditions such as lactose intolerance or celiac disease, but would play no role in this disease. (C) HIV is often a right answer on the examination, and chronic diarrhea is a common complaint in patients with HIV (for many reasons, including infection with Cryptosporidium, the use of antiretrovirals, etc.); however, the biopsy results confirm the diagnosis of Whipple disease. (E) Corticosteroids are the treatment of microscopic colitis, a cause of chronic diarrhea that will also have a normal appearance on colonoscopy. Biopsy will show normal architecture but many inflammatory cells, and staining with PAS would be negative.
A 51-year-old man with a history of poorly controlled diabetes mellitus presents to the Emergency Department with fever, headache, purulent nasal discharge, and decreased vision. The symptoms began in the morning and have rapidly progressed. The patient is now confused and lethargic. He is febrile and tachycardic, and physical examination reveals bilateral proptosis, perinasal swelling, and a large palatal eschar. His laboratory values are significant for a leukocyte count of 19,000/mm3 and a glucose of 468 mg/dL. His urine dipstick is positive for protein, glucose, and ketones. A biopsy is taken and confirms the diagnosis.
What is the most important next step in management?
Amphotericin B. Mucormycosis is a rapidly progressive infection caused most commonly by the fungi Mucor, Rhizopus, and Rhizomucor. While there are other presentations of mucormycosis (e.g., pulmonary and renal mucormycosis), the most common manifestation is infection of the nasal cavity that extends into the sinuses, orbits, and the brain and causes severe inflammation and necrosis. The main risk factor for this infection is immunosuppression, and a large proportion of patients are diabetic. It is common for diabetic patients with mucormycosis to have ketoacidosis. Though the prognosis is poor, rapid surgical debridement and antifungal therapy with amphotericin B provides the best outcomes. (A) Broad spectrum antibiotic regimens are not effective against these fungal species. (B) IV fluids and insulin will also be given to this patient, and managing the patient’s hyperglycemia and ketoacidosis will improve the outcome. However, the most important lifesaving therapy is surgery and antifungals, and this should not be delayed. (C) Deferoxamine is used as an iron chelator and actually increases the risk of mucormycosis.
An 83-year-old man is transferred to the hospital from his nursing home due to hypotension and confusion. He was previously well until yesterday morning, when the nursing staff observed that he seemed lethargic and spent the day in bed. Later that night, the staff tried to communicate with him but he was not oriented to place or time. His medical history is significant for hypertension, COPD, paroxysmal atrial fibrillation, and urinary incontinence requiring a urethral catheter. He is compliant with medications, has no recent medication changes, and has no sick contacts. On examination, his temperature is 35.4°C, his blood pressure is 68/44 mmHg, his heart rate is 88 beats per minute, and his respiratory rate is 18 breaths per minute. He is lethargic with flat neck veins; his cardiac examination is normal. His lungs are clear to auscultation, and there is no significant abdominal tenderness. His neurologic examination is normal, and his extremities are warm and well perfused. His laboratory values are significant for a leukocyte count of 13,500/mm3 and a serum lactate of 3.9 mmol/L (normal range 0.6 to 2.3 mmol/L). A urinalysis shows significant pyuria. A chest x-ray shows hyperinflated lungs but no focal opacities.
Which of the following is the most appropriate next step in management?
Rapid administration of normal saline. This patient meets SIRS criteria with a likely source of infection: urinary tract infection (UTI), which is suggested by pyuria. In addition, he is hypotensive with an elevated lactate, which indicates that this patient has severe sepsis. Although the management of sepsis is not tested in detail, it is useful to know some of the general principles. First, access should be obtained with two large-bore IVs and normal saline should be administered immediately (note that this would be harmful if the cause of shock is heart failure, so it is first important to diagnose the correct type of shock). (Administration of norepinephrine) If the patient’s blood pressure is not responding to heavy IV fluids (as per early goal-directed therapy targeting a mean arterial pressure ≥65 mmHg), then vasopressors can be given. Source control is also important; if there is an obvious source of infection, such as this patient’s urinary catheter, it should be removed immediately. (C) Empiric antibiotics should be started immediately, but preferably after two sets of blood cultures are obtained from separate venipuncture sites. Antibiotics should have broad coverage and be directed at the potential source of infection if possible. The combination of ceftriaxone and piperacillin-tazobactam is not a good regimen, since both are β-lactams; in addition, MRSA is a common cause of sepsis and is not being covered with this regimen. (D, E) Activated protein C is no longer recommended for the treatment of sepsis, and the benefit of hydrocortisone is unclear (it may be tried with hypotension refractory to IV fluids and vasopressors). (B) This patient is not in heart failure, as indicated by the low jugular venous pressure, and so diuresis with furosemide could be disastrous.
A 32-year-old woman suddenly develops abdominal pain and diarrhea. The abdominal pain is periumbilical and crampy, and she has had about 10 episodes of diarrhea per day over the past 3 days. She has no past medical or surgical history. She reports no sick contacts or recent travel, and no animal exposures. About 3 days ago she ate chicken at a barbecue that she thought might have been undercooked, but denies any other unusual food exposures. Stool studies are positive for fecal WBCs and fecal occult blood; stool culture eventually grows out Campylobacter jejuni. She is treated with IV fluids and ciprofloxacin and is discharged home. About 2 weeks later, she develops weakness and absent deep tendon reflexes involving the lower extremities bilaterally.
All of the following are also triggers for this complication, EXCEPT
Chlamydia trachomatis infection. This is a typical presentation of Campylobacter infection, which causes an acute inflammatory diarrhea indicated by the positive fecal leukocytes and RBCs. Common exposures include undercooked chicken and unpasteurized milk, and puppies and kittens can carry the organism. Campylobacter infection is a well-described trigger for Guillain–Barré syndrome (GBS), which presents as an acute ascending motor neuropathy (although there are variants, such as the Miller Fisher syndrome that presents as a descending neuropathy that may involve the cranial nerves). The pathogenesis is likely the result of antibody formation through the mechanism of molecular mimicry. (B, C, D) Preceding upper respiratory tract infections, HIV, and some vaccinations (influenza, meningococcal, etc.) are also associated with GBS. Chlamydia trachomatis infection is associated with reactive arthritis, not GBS. (Of note, Campylobacter and other enteric bacteria such as Salmonella, Shigella, Yersinia, and C. difficile can also cause reactive arthritis weeks after a diarrheal illness.)
A 32-year-old woman presents with recurrent dysuria. She was diagnosed with a UTI twice in the past 3 months, and was treated with 3 days of ciprofloxacin each time. The symptoms went away with treatment; however, they continue to recur. She currently complains of dysuria, frequency, and urgency similar to her previous episodes. Her previous urine culture results have all grown out Proteus mirabilis. A urine dipstick is positive for leukocyte esterase, nitrites, and blood; the urine pH is 8.1.
What is the most appropriate management of this patient?
CT scan of the abdomen and pelvis. UTIs are a common problem, and this patient presents with recurrent symptoms (dysuria, frequency, urgency) and signs (positive urine dipstick and culture) of cystitis. “Uncomplicated” cystitis refers to nonpregnant women without any structural or neurologic abnormalities and not immunosuppressed. The most frequent pathogens that cause uncomplicated UTIs are E. coli, Proteus, Klebsiella, and S. saprophyticus (especially in young, sexually active women). The fact that this patient has recurrent cystitis by Proteus raises the concern that there is a renal stone that might be acting as a nidus for recurrent infections. Proteus alkalinizes the urine with the enzyme urease and causes struvite stone formation (magnesium ammonium phosphate). Many of these stones are asymptomatic, but should be removed to prevent renal damage and recurrent infections.
(A, B) Oral ciprofloxacin and IV ceftriaxone are used to treat cystitis and pyelonephritis, respectively. (C) Self-treatment is an option for patients with recurrent cystitis; however, a urinary stone must first be ruled out in this patient given the frequency of Proteus infections. Risk factors for recurrent cystitis include the use of spermicide, frequent sexual intercourse, and any cause of decreased bladder emptying. (E) Reassurance is only appropriate in asymptomatic bacteriuria in nonpregnant patients.
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