Case 1: Blastomycosis-induced acute respiratory distress syndrome
By Dana Ley, ACP Medical Student Member, and Sarah Ahrens, MD, FACP
A 36-year-old man presented with 10 days of fevers, productive cough, and dyspnea. He was otherwise healthy and had no known history of lung disease. He had a smoking history of less than 10 pack-years and quit eight years before presentation. He lived in the Mississippi River basin but did not spend time in rural or densely wooded areas. He had no recent travel history.
On physical examination, the patient was in mild respiratory distress and afebrile, with a heart rate of 95 beats/min, a respiratory rate of 34 breaths/min, and normal blood pressure. He required bilevel positive-airway pressure (BiPAP) with 40% fraction of inspired oxygen (FiO2) to maintain normal oxygen saturation. Pulmonary exam was notable for decreased breath sounds with egophony on the right side. He had no rash or lesions. Initial labs were most remarkable for leukocytosis with bandemia. Influenza A and B tests were negative. A CT scan of the chest showed bilateral interstitial infiltrates, dense consolidation of the right lower and middle lobes, and an area concerning for intraparenchymal abscess in the right lower lobe (Figure 1).
The patient was admitted, and broad-spectrum antibiotics were initiated. His condition worsened, becoming febrile and ultimately requiring intubation. Sputum culture and smear demonstrated broad-based budding yeast (Figure 2), suggestive of Blastomyces dermatitidis. Blastomycosis urine antigen testing was positive. The patient was started on amphotericin B but continued to decline, developing acute respiratory distress syndrome (ARDS) and multisystem organ failure. He died one week after admission.
This patient had acute pulmonary blastomycosis and ARDS. Blastomyces dermatitidis is a fungus endemic to southeastern and south-central states that border the Mississippi and Ohio River basins and to the midwestern states that border the Great Lakes. Blastomycosis is contracted by inhalation of the fungal spores. Little data exist on the incidence of blastomycosis infection; in 2010, the state-specific age-adjusted hospitalization rate ranged from 0.05 to 2.9 per 100,000 person-years in the United States. However, this number is not thought representative of all cases, as most infections are do not require medical evaluation or hospitalization. The most frequent clinical presentation of blastomycosis is pulmonary infection. Less common manifestations include skin lesions, osteomyelitis, genitourinary infection, and central nervous system disease, including meningitis and intracranial abscess. Extra-pulmonary symptoms are typically manifest only when pneumonia is also present.
In one multicenter, retrospective study, a mortality rate of 12% was suggested for acute blastomycosis infection. Although blastomycosis is more severe in immunocompromised patients, it can also occur in the immunocompetent. Acute pneumonia due to blastomycosis mimics acute bacterial pneumonia and is characterized by fever, chills, and productive cough with or without hemoptysis. Sputum production is often copious and highly purulent. In rare instances, blastomycosis-induced pneumonia causes ARDS, and these cases have estimated in-hospital mortality rates as high as 50% to 89%. Unlike pulmonary histoplasmosis, blastomycosis pneumonia always requires treatment. According to the 2008 Infectious Diseases Society of America guidelines, itraconazole is first-line treatment for immunocompetent patients with mild to moderate pulmonary blastomycosis. Severe blastomycosis infection is defined as severe pulmonary disease, disseminated extrapulmonary disease, central nervous system involvement, infection in immunosuppressed or pregnant patients. Severe disease is treated with liposomal amphotericin B.
- Blastomycosis infections may occur in immunocompetent hosts, most commonly manifest as a pulmonary infection.
- Pulmonary blastomycosis is rarely associated with ARDS, which, when it occurs, carries a high risk of in-hospital mortality.
Case 2: Medication-associated microscopic colitis
By Farah Acher Kaiksow, MD, MPP, ACP Member
A 71-year-old man presented with three weeks of watery, nonbloody diarrhea. He reported having at least four episodes daily, each after oral intake, and not associated with abdominal pain or cramping. The diarrhea ceased if he stopped eating and drinking. The patient reported no sick contacts, changes in diet, recent travel or antibiotic use. His medical history included a diagnosis of gastroesophageal reflux disease; he had previously been treated with a proton-pump inhibitor (PPI) but was switched to ranitidine. Colonoscopy and esophagogastroduodenoscopy (EGD), both within the past three years, were unremarkable.
On presentation, the patient's vital signs were normal. He was a well-appearing elderly man with normal cardiac and pulmonary exams. His abdomen exhibited diffuse tenderness to deep palpation. Chemistry panel was notable for an elevated creatinine level at 2.23 mg/dL (reference range, 0.67 to 1.17 mg/dL), a potassium level of 3.2 mmol/L (reference range, 3.5 to 4.7 mmol/L), and a magnesium level of 1.6 mg/dL (reference range, 1.7 to 2.4 mg/dL). Stool studies were negative, including testing for Clostridium difficile. Electrolytes normalized with repletion and volume-related renal injury resolved with intravenous fluids. After the patient's diarrhea did not subside with two days of loperamide, a colonoscopy with biopsies revealed colonic mucosa with increased chronic inflammation of the lamina propria and focal cryptitis. The patient's ranitidine was stopped, budesonide was started, and the patient's symptoms resolved over the following few days.
The diagnosis in this case is lymphocytic colitis, presumably medication-induced and related to ranitidine use. Lymphocytic colitis, along with collagenous colitis, is a subtype of microscopic colitis, a chronic inflammatory disease of the colon. Microscopic colitis is more common in women and typically presents with profuse, watery, and nonbloody diarrhea. Diagnosis is made via biopsy, which in lymphocytic colitis shows lymphocytic infiltration of the lamina propria as opposed to the thick band of subepithelial collagen noted in collagenous colitis. The exact etiology of microscopic colitis is not known, although studies suggest that genetics, medications, and smoking may contribute. Many of the medications associated with microscopic colitis are common, including aspirin, NSAIDs, PPIs, sertraline, and ranitidine. Other histamine-receptor blockers have not been similarly implicated. Initial treatment is risk-factor modification and loperamide, with oral budesonide used as second-line therapy. Microscopic colitis usually resolves with (and sometimes without) treatment, but relapse is seen in at least 25% of patients.
- Lymphocytic colitis and collagenous colitis are the two subtypes of microscopic colitis, which causes chronic diarrhea.
- Common medications are associated with microscopic colitis, including aspirin, NSAIDs, PPIs, sertraline, and ranitidine.
Case 3: Primary aldosteronism
By Scott Wilson, DO, FACP
A 28-year-old woman presented with two months of intermittent emesis, photophobia, frontal headaches, and malaise. She had no significant medical history. She exercised regularly, consumed minimal alcohol, occasionally smoked cigarettes, and reported no use of illegal drugs. Relevant family history included hypertension in her mother. Review of systems was positive for intermittent palpitations and diaphoresis and negative for weight or appetite changes, diarrhea, chest pain, dizziness, menstrual changes, or muscle weakness.
On presentation, her vital signs were significant for a blood pressure of 216/148 mm Hg; all other signs were normal. The patient's physical exam was unremarkable, with normal female hair distribution, no lymphadenopathy, no thyroid abnormalities, and no evidence of dorsocervical fat pad. Her skin was without rash, hyperpigmentation, or striae. Testing of cranial nerves, muscular strength, and sensation were all normal. Basic metabolic panel was notable for a very low potassium level of 2.0 mmol/L (reference range, 3.5 to 5.1 mmol/L) but was otherwise normal. Further testing revealed normal levels of thyroid-stimulating hormone, cortisol, and dehydroepiandrosterone (DHEA) and a negative urine drug screen. An overnight dexamethasone suppression test was normal. The patient had a significantly elevated serum aldosterone-to-renin ratio of 99 (reference range, <25). An abdominal MRI showed a 2.4 × 1.2-cm lipid-rich right adrenal adenoma. The patient underwent a curative adrenalectomy. She was started on amlodipine, her blood pressure normalized, and her symptoms resolved.
The diagnosis in this patient is primary aldosteronism (PA) from an aldosterone-producing adrenal adenoma. PA exposes patients to higher risk of cardiovascular complications compared to age-matched patients with essential hypertension. Previously, PA was believed to occur in fewer than 1% of patients with hypertension. However, the true prevalence of PA is likely underestimated because hypokalemia does not always occur, and thus the condition frequently remains undetected. Prospective studies using updated screening methods suggest PA is more common than previously thought, with some studies suggesting that more than 10% of all patients with hypertension may have this treatable condition. Aldosterone-producing adrenal adenomas and bilateral adrenal hyperplasia are the most common causes of PA. According to the 2016 Endocrine Society Clinical Practice Guidelines, aldosterone-renin ratio testing is recommended in patients with the following: blood pressures over 140/90 mm Hg and hypokalemia, resistant hypertension, hypertension and an adrenal “incidentaloma,” hypertension and sleep apnea, or hypertension and a family history of early-onset hypertension. Such testing is not recommended in older patients with mild hypertension or normokalemia or those in whom treatment would not be considered.
Plasma aldosterone-to-renin ratio is the best laboratory test to identify primary aldosteronism. If plasma renin levels are below detection and plasma aldosterone levels are greater than 20 ng/dL, the diagnostic evaluation can proceed directly to CT, which is often superior to MRI due to superior spatial resolution. In all other cases, confirmatory testing is recommended via percutaneous adrenal venous sampling, which distinguishes between unilateral and bilateral causes of hyperaldosteronism. If imaging or venous sampling confirms a unilateral cause, treatment is unilateral adrenalectomy; bilateral adrenal hyperplasia is treated with mineralocorticoid receptor antagonist therapy. Most patients who undergo surgery are cured or have substantially reduced needs for antihypertensive medications.
- PA, a treatable form of secondary hypertension, is more common than previously thought and is most reliably detected via plasma aldosterone-to-renin ratio.
- If imaging or venous sampling confirms a unilateral cause of PA, treatment is unilateral adrenalectomy; bilateral adrenal hyperplasia is treated with mineralocorticoid receptor antagonist therapy.
Case 4: Brugada syndrome
By Sean M. O’Neill, MD, FACP
A 60-year-old man presented with several days of diarrhea, fevers, and syncope. His medical history was significant for recurrent syncopal episodes since his teenage years, all of which occurred during times of self-resolving illness. Review of systems was negative for chest pain or other cardiac symptoms. His vital signs were normal except for a temperature of 39 °C. An electrocardiogram (EKG) (Figure 3) showed “coved-type” ST elevation in leads V1 and V2. Initial troponin level was 0.05 ng/mL (reference range, 0.00 to 0.03 ng/mL). Once the patient's fever resolved, a repeat EKG showed resolution of the ST elevations. Telemetry was normal for the remainder of his hospitalization, and transthoracic echocardiogram was within normal limits. Stool culture eventually grew Campylobacter jejuni. Given the patient's history of recurrent syncope and transient EKG changes, a procainamide challenge was performed. The patient underwent implantable cardioverter defibrillator (ICD) placement and was referred for genetic counseling.
This patient was diagnosed with Brugada syndrome after presenting with recurrent syncope while febrile (in this case, due to a Campylobacter infection) and transient characteristic EKG changes. Brugada syndrome is an autosomal-dominant genetic disorder with variable expression, characterized by EKG findings of pseudo-right bundle-branch block and one of two types of ST elevation in leads V1 and V2: Type 1 pattern shows “coved-type” ST elevation, as in this case, while the elevations seen in type 2 pattern are described as “saddle-back.” The EKG changes in Brugada syndrome can be transient and provoked by fever, medications, cocaine, and alcohol.
Brugada syndrome is rare, with prevalence rates less than 0.5% in the United States, but is associated with sudden cardiac death from ventricular tachyarrhythmias. Patients with transient EKG changes consistent with a Brugada pattern should be evaluated further for the clinical symptoms of Brugada syndrome and electrophysiology consultation should be considered. A drug challenge with a sodium-channel blocker such as procainamide can help to risk stratify patients with Brugada pattern in presence of equivocal symptoms at centers with the necessary expertise to do so. There is no current consensus regarding prognostic capability of invasive electrophysiological testing in asymptomatic patients. ICD implantation is indicated in patients with confirmed Brugada syndrome, with select antiarrhythmics (amiodarone, quinidine) used as second-line treatment. This patient's recurrent syncope while febrile was presumed to be cardiac in nature, and he was thus a candidate for ICD implantation.
- Brugada syndrome is a genetic disorder diagnosed when characteristic EKG changes are present along with symptoms such as syncope or cardiac arrest.
- The characteristic EKG changes of Brugada syndrome can be transient and provoked by infection, medications, illicit drugs, or alcohol.