Cases from Saint Agnes Hospital

Drug-induced aseptic meningitis, hypothyroidism as a reversible cause of cardiomyopathy, unintentional salicylate overdose, and more.

Case 1: Drug-induced aseptic meningitis from cetuximab

By Hayder Abbood, MD, ACP Resident/Fellow Member, and Uqba Khan, MD, ACP Member

The patient

A 40-year-old woman with a history of recently diagnosed metastatic colon cancer presented reporting a severe headache for 4 hours after having received her second cycle of cetuximab earlier that morning. She described the headache as a bifrontal, throbbing pain with 10/10 intensity associated with photophobia, nausea, and vomiting. She had been evaluated for similar symptoms 1 month prior to this admission after receiving her first cycle of cetuximab; at that time, despite a negative cerebrospinal fluid (CSF) culture, she was presumptively diagnosed with bacterial meningitis, and she completed a course of empiric antibiotic therapy. Vital signs on current presentation were unremarkable except for a low-grade fever, with a temperature of 100.1 °F. Physical examination revealed mild neck stiffness and no focal neurological deficits.

Laboratory testing revealed a white blood cell count of 3,200 cells/µL, a hemoglobin level of 12.6 g/dL, and a platelet count of 101,000/µL. Urine toxicology was negative. A CT of the brain demonstrated no acute intracranial findings. Lumbar puncture revealed marked pleocytosis (white blood cell count, 5,540 cells/µL), 97% polymorphonuclear cell predominance, and negative Gram stain. CSF glucose level was decreased at 46 mg/dL, and protein level was elevated to 123 mg/dL. Bacterial cultures, polymerase chain reaction for herpes simplex virus DNA, and cryptococcal antigen testing were all negative. Subsequent MRI of the brain was normal with no evidence of enhancing parenchymal lesions.

The diagnosis

This patient's diagnosis is drug-induced aseptic meningitis due to cetuximab. Drugs known to commonly cause drug-induced aseptic meningitis include nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulin, intrathecal agents, and vaccines. There are 2 proposed mechanisms of drug-induced aseptic meningitis: a delayed-type hypersensitivity reaction and direct meningeal irritation. Drug-induced aseptic meningitis can sometimes be difficult to differentiate from bacterial meningitis, especially when the CSF profile is inflammatory. Polymorphonuclear cells generally predominate, CSF glucose levels are usually normal or decreased, and protein levels are usually elevated. All cultures, including CSF cultures, must be negative for any bacterial, viral, or fungal etiologies. Drug-induced aseptic meningitis is typically self-limiting, with primary treatment being supportive care and withdrawal of the culprit drug. Recovery is usually complete within days to weeks after drug therapy is discontinued.

Cetuximab is a chimeric antiepidermal growth factor receptor (EGFR) monoclonal antibody that has been approved by the FDA for the treatment of metastatic colon cancer (when it is K-Ras negative and EGFR positive) and head and neck cancers. Side effects most commonly associated with cetuximab therapy include infusion-related reactions, rash, fatigue, malaise, and nausea. The evidence linking cetuximab to drug-induced aseptic meningitis comes from post-marketing experience; it is a rare complication. Rechallenging the patient with cetuximab may be considered, although there is a risk of recurrence. Case reports have suggested that premedicating patients with intravenous steroids and antihistamines and slowing the rate of infusion might prevent the recurrence of aseptic meningitis.

This patient made a full neurologic recovery and continued to receive cetuximab therapy for her malignancy.


  • Drug-induced aseptic meningitis typically shows a CSF pleocytosis with polymorphonuclear cell predominance and is a diagnosis of exclusion that can be difficult to discern from acute bacterial meningitis.
  • Cetuximab is a rare but well-documented cause of drug-induced aseptic meningitis and meningeal symptoms in patients receiving this medication should raise suspicion for this entity.

Case 2: Hypothyroidism as a reversible cause of cardiomyopathy

By Hayder Abbood, MD, ACP Resident/Fellow Member; Naser Gharaibeh, MD, ACP Resident/Fellow Member; Shadi Barakat, MD, ACP Member; and Lauren Kleess, MD, ACP Resident/Fellow Member

The patient

A 45-year-old woman with a history of hypothyroidism and medication nonadherence (she had been off thyroid replacement for approximately 6 to 8 months) presented with shortness of breath, orthopnea, and bilateral lower-extremity edema for 2 weeks. She reported generalized body weakness with loss of energy, cold intolerance, and an unintentional weight gain of 40 pounds over the previous 3 to 4 months. Vital signs on admission revealed a normal pulse and blood pressure. Physical examination was most notable for bradykinesia, delayed deep tendon reflexes, bilateral basilar rales on pulmonary examination, and 2+ bilateral lower-extremity edema. Notable laboratory values on admission include a thyroid-stimulating hormone level of 44.5 µIU/mL (reference range, 0.5 to 4.70 µIU/mL) with a free thyroxine level of 0.09 ng/dL (reference range, 0.8 to 1.8 µIU/mL) and an elevated B-type natriuretic peptide (BNP) level of 496 pg/mL.

Echocardiogram demonstrated a reduced ejection fraction of 10% with global hypokinesis, significant left-sided dilatation, and circumferential pericardial effusion. Cardiac catheterization showed no evidence of coronary disease. Intravenous levothyroxine therapy was initiated in addition to standard treatments for heart failure, with clinical improvement. Upon outpatient follow-up 1 month after discharge, the patient noted marked improvement in her symptoms. Repeat echocardiography 2 months following discharge showed a significantly improved ejection fraction of 40%.

The diagnosis

This patient's diagnosis is hypothyroid-induced cardiomyopathy. Thyroid hormone, via effects at a cellular level, plays a significant role in cardiovascular function. The primary abnormalities encountered in the hypothyroid state include bradycardia, an increase in peripheral vascular resistance, and decreased contractility and cardiac output. In severe hypothyroidism, low cardiac output develops due to bradycardia, decreased ventricular filling, and decreased cardiac contractility. This can be potentiated by pericardial effusion, which occurs in an estimated 25% of hypothyroid patients and may be large. However, decompensated heart failure is rare due to a commensurate reduction in peripheral tissue oxygen consumption also encountered in the hypothyroid state.

There are no reliable data on the frequency of hypothyroidism complicated by heart failure. In terms of prognosis, a study from 2006 found no increase in all-cause mortality in over 15,000 patients treated for hypothyroidism, although there was an increased risk for cardiovascular morbidity, defined as nonfatal stroke and myocardial infarction. Thyroxine replacement has been reported to improve cardiac contractility in hypothyroid patients, and other case reports of “myxedema cardiomyopathy” have documented substantial improvement in cardiac function once a euthyroid state is re-established.


  • Hypothyroidism is a rare but reversible cause of dilated cardiomyopathy.
  • In thyroid-related dilated cardiomyopathy, treatment with levothyroxine can significantly improve myocardial function.

Case 3: Unintentional salicylate overdose

By Mustafa Abdulmahdi, MD, ACP Resident/Fellow Member; Aimaz Afrough, ACP Resident/Fellow Member; Ammer Bekele, MD; and Shahad Ali, MD

The patient

A 50-year-old woman with a history of migraine headaches presented with an “excruciating” headache for 1 week. She described the pain as throbbing and nonradiating, localized to the right side of her head, and excruciating with 10/10 intensity. There was associated nausea and vomiting. Further history revealed that she had been treating her pain at home with an extra-strength over-the-counter pain medication (which contained 520 mg of aspirin, 260 mg of acetaminophen, and 32.5 mg of caffeine). She had taken 20 doses over a 12-hour period during the day before presentation. On the day of presentation, she developed severe nausea with several episodes of emesis.

On initial assessment, vital signs were normal. Her physical examination revealed poor oral hygiene with dental caries, irritability and agitation, resting tremor, and photophobia. Laboratory findings revealed an elevated anion gap of 18 and a decreased bicarbonate level of 13.7 mEq/L. Arterial blood gas testing showed a pH of 7.43, partial pressure of CO2 of 21 mm Hg, and partial pressure of oxygen of 133 mm Hg, consistent with a respiratory alkalosis. Liver and thyroid function tests were unremarkable, and urine toxicology screen was negative. Serum salicylate level was 47 mg/dL (greater than 30 mg/dL is considered toxic). With appropriate therapy, her symptoms and laboratory abnormalities normalized within 48 hours of initial presentation.

The diagnosis

This patient was diagnosed with unintentional salicylate toxicity. Salicylate toxicity should be suspected in patients with a history of previous overdose, repeated ingestion of therapeutic doses, or unexplained mixed metabolic acidosis and respiratory alkalosis. Early symptoms include nausea, vomiting, tinnitus, and hyperventilation; late symptoms include hyperactivity, fever, confusion, and seizures. During the first few hours after ingestion, an arterial blood gas usually shows primary respiratory alkalosis followed by mixed metabolic acidosis/respiratory alkalosis. Salicylate causes metabolic acidosis by multiple mechanisms: impaired aerobic metabolism, inhibition of the citric acid cycle, and an increase in the metabolism of fatty acids. Salicylate also stimulates respiratory centers in the medulla, causing primary respiratory alkalosis. The serum salicylate level is helpful in confirming the diagnosis, and serial measurements help determine whether absorption is ongoing. Treatment includes activated charcoal to prevent absorption (if ingestion was recent) and alkaline diuresis. Bicarbonate is the mainstay of therapy because it treats acidemia and promotes salicylate elimination by the kidneys; the goal is to increase the urine pH to 7.5 to 8.0. Hemodialysis, intubation, and mechanical ventilation may be required in severe cases.


  • Salicylate toxicity should be suspected in patients presenting with a possible intentional or unintentional ingestion along with a mixed acid-base status, which includes an anion-gap metabolic acidosis and respiratory alkalosis.
  • A high index of suspicion must be maintained for salicylate toxicity as patients might not be aware of salicylate content of various over-the-counter products.

Case 4: Postpartum preeclampsia

By Lauren Kleess, MD, ACP Resident/Fellow Member, and Ricardo Conti, MD, ACP Member

The patient

A 36-year-old woman presented with chest pain and shortness of breath 4 days after delivering a healthy baby. The peripartum period had been complicated by influenza, for which she was successfully treated. Vital signs revealed hypertension (blood pressure of 175/86 mmHg) and hypoxemia (oxygen saturation of 96% on 2 L nasal cannula). Physical examination was notable for bilateral inspiratory crackles and 2+ bilateral pitting edema. Laboratory results revealed elevated aminotransferase levels (aspartate aminotransferase, 126 U/L; alanine aminotransferase, 129 U/L), normal total bilirubin, and normal renal function. Urinalysis was without proteinuria or casts. Complete blood cell counts and peripheral blood smear were unremarkable. Chest X-ray was suggestive of pulmonary edema. CT of the chest ruled out pulmonary embolus and confirmed pulmonary edema. In addition to diuresis with furosemide, she underwent an echocardiogram, which showed normal systolic and diastolic function without regional wall motion abnormality.

Within several hours, her blood pressure peaked at 198/86 mmHg and she developed headache and double vision. A brain MRI at this time was normal. She was loaded with fosphenytoin for seizure prophylaxis and started on hydralazine for acute blood pressure control. With this regimen, her condition stabilized: blood pressure improved, her double vision with headache resolved, and no seizure activity was noted. The patient was monitored overnight and remained stable. She was discharged home on chlorthalidone; fosphenytoin was discontinued.

The diagnosis

This patient was diagnosed with postpartum preeclampsia. She had new-onset hypertension with associated pulmonary edema, headache, and double vision, consistent with the new American Congress of Obstetricians & Gynecologists diagnostic criteria. Preeclampsia and eclampsia are enigmatic syndromes with complex pathophysiology. The primary cause is abnormal placentation, which ultimately causes endothelial dysfunction in the mother. Preeclampsia complicates 5% to 8% of pregnancies. Preeclampsia has been classically defined by the presence of hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) and proteinuria occurring after 20 weeks of gestation or within 48 hours after delivery. However, the diagnostic criteria have been changed and proteinuria is no longer a requirement if additional findings suggestive of end-organ damage are present, including thrombocytopenia (platelet count <100,000/µL, renal insufficiency (serum creatinine level ≥1.1 mg/dL or doubling of serum creatinine levels in absence of other renal disease), serum liver aminotransferase levels elevated to at least twice the upper limit of normal, pulmonary edema, or cerebral or visual symptoms. Additionally, this disease can occur up to 6 weeks after delivery.

HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome and PRES (posterior reversible encephalopathy syndrome) are diagnostic alternatives to consider. Magnesium sulfate is the treatment of choice to prevent seizures in preeclampsia but has been associated with pulmonary edema, hence this patient was treated with an antiepileptic medication and monitored closely.


  • The diagnostic criteria for preeclampsia have been expanded to include other evidence of end-organ damage along with new-onset hypertension when proteinuria is absent.
  • Preeclampsia classically occurs after 20 weeks of gestation, but it can present up to 6 weeks postpartum.

Case 5: Legionnaires' disease

By Lauren Kleess, MD, ACP Resident/Fellow Member; Robert Ross, MD; and Dean Meadows, MD

The patient

A 76-year-old woman with a history of diabetes and chronic kidney disease (baseline creatinine level, 1.5 mg/dL) presented with shortness of breath and an altered mental status. She reported a dry cough, subjective fevers and chills, and diarrhea with 2 or 3 episodes of loose “green” stool for 2 days. She became increasingly confused after initial presentation. Vital signs demonstrated fever and significant hypoxemia with an oxygen saturation of 82% on room air. Crackles were noted on examination at the right lung base. Notable laboratory studies included white blood cell count of 16,300 cells/µL with 16% bands, a sodium level of 127 mEq/L, acute kidney injury (creatinine level, 2.6 mg/dL), an aspartate aminotransferase level of 123 U/L, and an alanine aminotransferase level of 56 U/L. Chest X-ray showed a right-sided pleural effusion with right basilar consolidation (Figure). The patient was intubated, started on broad-spectrum intravenous antibiotics, and admitted to the ICU. The urinary antigen for Legionella was positive. Intravenous levofloxacin, renally adjusted, was added for additional coverage against Legionella pneumophilia. Bronchoalveolar lavage revealed a positive culture for Legionella. The ICU course was further complicated by septic shock and oliguric renal failure requiring renal replacement therapy. The patient improved with supportive care and was eventually extubated. Renal function improved, and hemodialysis was discontinued.

The diagnosis

This patient's diagnosis is Legionnaires' disease, the pneumonia caused by Legionella pneumophila. Legionella is a known sporadic cause of community-acquired pneumonia but is also associated with outbreaks from environmental sources. Environmental reservoirs can include contaminated showers, faucets, and cooling towers. Patients with pneumonia from Legionella can present with neurologic symptoms, gastrointestinal symptoms, hyponatremia, or elevated aminotransferase levels; however, these findings are not pathognomonic. Urinary antigen testing is rapid and widely available although it only detects L. pneumophilia serogroup 1, which accounts for 50% to 70% of cases of Legionnaires' disease. The diagnosis should be confirmed by sputum culture as soon as possible, because molecular testing can assist the evaluation of environmental sources. Legionellosis is treated with either a macrolide or fluoroquinolone. While there are no randomized controlled trials to compare these classes, observational data suggest that for patients with mild-to-moderate pneumonia, there is no significant difference between groups. However, for patients with severe pneumonia, levofloxacin may be superior, with fewer complications and shorter duration of hospitalization. Patients with chronic medical conditions are at increased risk for complications from Legionnaires' disease.


  • Legionnaires' disease, the pneumonia caused by Legionella pneumophila, can be accompanied by neurologic symptoms, gastrointestinal symptoms, hyponatremia, or elevated aminotransferase levels.
  • Analysis of respiratory samples by Legionella culture is critical for investigation of outbreaks and identification of environmental sources.