A Young Woman's Medical Mystery: From Headache to Multi-Organ Failure

Table of Contents

• Introduction: A Sudden Onset of Symptoms
• Case Presentation: The Patient's Story
• Initial Evaluation and Hospital Course
• Transfer to Specialized Care
• Detailed Imaging Findings
• Laboratory Results Analysis
• Differential Diagnosis: What Could This Be?
• Final Diagnosis and Treatment
• Clinical Implications for Patients
• Key Lessons from This Case
• Source Information

Introduction: A Sudden Onset of Symptoms

This case involves a previously healthy 22-year-old woman who developed a rapidly progressive illness that began with seemingly minor symptoms but quickly escalated to life-threatening multi-organ failure. Her case demonstrates how quickly a bacterial infection can spread throughout the body and cause damage to multiple systems, including the brain, heart, lungs, and spleen.

The patient's story highlights the importance of recognizing concerning symptoms early and seeking appropriate medical care. Her case was particularly challenging because she presented with symptoms affecting multiple body systems simultaneously, requiring doctors to consider various possible diagnoses before identifying the underlying cause.

Case Presentation: The Patient's Story

The patient was a 22-year-old woman who worked in healthcare and had been in excellent health until eight days before her hospitalization. Her symptoms began with nausea and muscle aches (myalgias), which progressed over the next two days to include chills, vomiting, neck pain, and a headache with sensitivity to sound (sonophobia).

She initially visited an emergency department where doctors noted she had dry mucous membranes but no signs of meningitis. Her white blood cell count was elevated at 12,300 per microliter (normal range: 4,800-10,800), and her platelet count was low at 95,000 per microliter (normal range: 150,000-450,000). She received intravenous fluids and pain medication and was sent home with a diagnosis of presumed viral syndrome.

Initial Evaluation and Hospital Course

Over the next week, her symptoms worsened significantly. She developed increased headache with new sensitivity to light (photophobia), along with general malaise, loss of appetite, nonproductive cough, and shortness of breath with minimal exertion. Two days before transfer to the specialized hospital, her mother noticed episodes of confusion with nonsensical speech and excessive sleepiness.

When she returned to the emergency department, her vital signs showed fever (38.0°C), rapid heart rate (106 beats per minute), low blood pressure (100/55 mm Hg), and rapid breathing (22 breaths per minute). Her oxygen saturation was 97% while receiving supplemental oxygen. Doctors noted photophobia, mild throat redness, and diffuse abdominal tenderness.

Initial CT scanning of her head without contrast showed evidence of subarachnoid hemorrhage (bleeding around the brain) and diffuse ischemic changes in the parietal and temporal lobes. CT scans of her chest, abdomen, and pelvis showed:

• Diffuse interstitial lung markings
• Multiple opacities and nodules in the peripheral lungs
• Two hypodensities in the peripheral spleen
• Small retroperitoneal lymph node enlargement

Transfer to Specialized Care

The patient was admitted to the intensive care unit and started on multiple antibiotics including vancomycin, ceftriaxone, metronidazole, and doxycycline. Despite treatment, her breathing worsened, requiring increased oxygen support. She was then transferred to Massachusetts General Hospital for specialized care.

Upon arrival, she was confused and breathing rapidly. Her medical history included depression treated with citalopram. She reported social wine drinking, electronic cigarette use, and occasional marijuana use but no tobacco smoking. She had traveled to the Caribbean over a year earlier but had no recent exposures to wooded areas, animals, or insects.

Examination revealed she was in respiratory distress using accessory muscles to breathe. She was only oriented after prompting and had neck stiffness (meningismus) and shoulder rigidity. Doctors heard abnormal lung sounds (rales and rhonchi) and a grade 3/6 holosystolic heart murmur loudest at the apex and left armpit area, radiating to the sternum. Her spleen tip was palpable, and she had a small patch of small red spots (petechiae) on her upper chest.

Detailed Imaging Findings

Advanced imaging revealed multiple serious abnormalities throughout her body:

Head CT and MRI: Showed evidence of acute subarachnoid hemorrhage and multiple acute cortical infarcts (strokes) in both brain hemispheres. Specifically, there were bilateral scattered curvilinear hyperdensities in the cortical sulci suggesting bleeding, and focal hypodense regions in the left superior parietal lobule and right temporal lobe suggesting strokes.

Chest CT: Revealed mild interstitial edema, bilateral pleural effusions, and multifocal peribronchovascular nodular opacities and consolidations involving all lung lobes. Some lesions were peripherally distributed without cavitation.

Abdominal CT: Showed several splenic hypodensities most likely representing splenic infarcts (areas of dead tissue in the spleen due to blocked blood flow), with accompanying mild ascites and mild periportal edema.

A lumbar puncture (spinal tap) performed after platelet transfusion showed an opening pressure of 38 cm of water (elevated), with cerebrospinal fluid containing: - Glucose: 41 mg/dL (low, normal 50-75) - Protein: 31 mg/dL (normal) - Red blood cells: 2400/μL (elevated, normal 0-5) - White blood cells: 49/μL (elevated, normal 0-5) with 76% neutrophils

Laboratory Results Analysis

The patient's laboratory tests showed multiple abnormalities that evolved over her illness:

Blood counts: Showed progressive anemia (hemoglobin dropped from 12.5 to 8.9 g/dL), persistent elevated white blood cell count (peaking at 20,210/μL with 92% neutrophils), and severe thrombocytopenia (platelets dropped to 28,000/μL before transfusion). Her peripheral blood smear showed toxic granulation.

Chemistry tests: Revealed low sodium (133-136 mmol/L), low potassium (3.4 mmol/L), elevated urea nitrogen (25 mg/dL), normal creatinine, low calcium (7.7-8.0 mg/dL), low total protein and albumin, elevated alkaline phosphatase (169 U/L), and elevated bilirubin (1.8 mg/dL).

Cardiac markers: N-terminal pro-B-type natriuretic peptide was dramatically elevated at 9130 pg/mL (normal <125), indicating heart strain.

Inflammation markers: d-Dimer was elevated at 1406 ng/mL (normal <500), fibrinogen was 502 mg/dL (normal 150-400), and ferritin was 258 μg/L (normal 10-200).

Differential Diagnosis: What Could This Be?

Doctors considered multiple possible explanations for this complex presentation:

Infectious causes: The combination of fever, heart murmur, neurological symptoms, and multi-organ involvement strongly suggested an infectious process. Possible candidates included: - Bacterial endocarditis (heart valve infection) - Tick-borne illnesses (Rocky Mountain spotted fever, ehrlichiosis, anaplasmosis) - Viral infections (though initial testing was negative) - unusual bacterial infections (leptospirosis, brucellosis)

Autoimmune disorders: Given her family history of autoimmune diseases (mother with cutaneous lupus, grandmother with Hashimoto's thyroiditis), doctors considered autoimmune causes like lupus-related Libman-Sacks endocarditis or antiphospholipid syndrome, though initial testing for antinuclear antibodies was negative.

Other considerations: Thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome were considered but seemed less likely given the absence of characteristic lab findings.

The presence of a heart murmur, neurological symptoms, respiratory failure, spleen abnormalities, and blood culture results ultimately pointed most strongly toward infectious endocarditis with septic embolization (infection spreading through the bloodstream causing blockages in various organs).

Final Diagnosis and Treatment

The definitive diagnosis was established through blood cultures that grew Streptococcus mitis, a type of bacteria that is part of the normal mouth flora but can cause serious infections when it enters the bloodstream.

Transesophageal echocardiogram (a specialized ultrasound through the esophagus) revealed the source: multiple vegetations (infected clumps of material) on the mitral valve, with several perforations in the posterior leaflet causing severe mitral regurgitation (leaking). This explained the heart murmur and how bacteria were spreading throughout her body.

Treatment involved: - Continued broad-spectrum antibiotics - Surgical consultation for possible valve repair or replacement - Supportive care including mechanical ventilation - Management of complications including seizures and neurological deficits

The Streptococcus mitis infection was particularly aggressive because this bacterium can produce a toxin that causes widespread inflammation and tissue damage throughout the body.

Clinical Implications for Patients

This case offers several important lessons for patients:

Recognizing serious symptoms: What began as seemingly minor flu-like symptoms rapidly progressed to life-threatening illness. Patients should seek prompt medical attention for:

• Severe headaches with light or sound sensitivity
• Fever that persists or worsens
• Confusion or changes in mental status
• Shortness of breath with minimal exertion
• Unexplained bruising or small red spots on skin

Understanding endocarditis risk: While endocarditis can affect anyone, it's more common in people with: - Previous heart valve damage or artificial valves - Certain congenital heart conditions - History of intravenous drug use - Recent dental procedures or other medical procedures that can introduce bacteria into the bloodstream

Importance of complete medical history: This patient's healthcare occupation might have exposed her to pathogens, though the exact source of her infection wasn't identified.

Key Lessons from This Case

This complex case illustrates several critical medical principles:

Multi-system evaluation: When patients present with symptoms affecting multiple organ systems simultaneously, doctors must consider diagnoses that can explain all findings rather than treating each symptom in isolation.

Rapid progression: Some bacterial infections can progress with alarming speed from mild symptoms to life-threatening multi-organ failure. Early recognition and treatment are essential.

Diagnostic challenges: This case required coordination between multiple specialists including infectious disease, cardiology, neurology, and critical care physicians to reach the correct diagnosis.

Treatment complexity: Managing such severe infections requires both targeted antibiotic therapy and supportive care for the various complications that arise from widespread inflammation and organ damage.

The patient ultimately required prolonged hospitalization with intensive care support, multiple antibiotics, and likely will need long-term follow-up for her neurological and cardiac complications.

Source Information

Original Article Title: Case 38-2024: A 22-Year-Old Woman with Headache, Fever, and Respiratory Failure

Authors: Eleftherios Mylonakis, M.D., Ph.D., Eric W. Zhang, M.D., Philippe B. Bertrand, M.D., Ph.D., M. Edip Gurol, M.D., Virginia A. Triant, M.D., M.P.H., and Kristine M. Chaudet, M.D.

Publication: The New England Journal of Medicine, December 5, 2024; 391:2148-57

DOI: 10.1056/NEJMcpc2100279

This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital.