A rare case of Adult Still’s Disease

Our wonderful medical student Tae presented a very interesting case today: a middle-aged male with no past medical history who presented with acute left knee pain and effusion, fevers, and leukocytosis. 

With any monoarticular, painful joint effusion without a history of trauma, arthrocentesis should be performed to rule out septic arthritis and look for crystalline arthropathies (gout and pseudogout). This patient’s synovial fluid showed 10 thousand WBCs with >75% neutrophils.

Interpretation of synovial fluid studies: When interpreting synovial fluid studies, many factors should be taken into consideration. The general cutoffs for WBC count in the fluid are guidelines, but there is significant overlap between categories.

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When differentiating between noninfectious inflammatory arthritides and septic arthritis, the distinction is not clear cut. The more WBCs you see in the joint fluid, the more likely it is to be a septic joint (>50,000 WBC is typical), but immunocompromise can decrease the WBC count and early in the course of septic arthritis, counts may be lower. Noninfectious inflammatory arthritis can have WBC counts >50,000 as well so history and other clinical data must be taken into account.

In this patient’s case, the WBC count of only 10 thousand falls in the classical non-infectious, inflammatory arthritis range. Gram stain did not show any organisms, but cultures grew rare growth Strep viridans and Actinomyces after more than 3 days in the micro lab. Outside of hematogenous spread of polymicrobial bacteremia and direct penetrating trauma to the joint, polymicrobial septic arthritis is exceedingly rare. Although all of this cast doubt on the diagnosis of septic arthritis, the patient was treated with Vancomycin and Zosyn initially, then narrowed to Zosyn alone. However, fevers continued, WBC count rose from 21 to 31, and procalcitonin increased from 0.83 to over 5.  A second arthrocentesis was performed, which showed a WBC count of only 30 thousand and no organisms on gram stain with a negative culture. He was subsequently taken to the operating room for arthroscopic drainage and debridement, which did not yield any pus. The orthopedic surgery team deemed the knee to not be a septic joint and did not think bacterial joint infectious could be responsible for his worsening condition.

On review of systems, the patient also endorsed some mild left elbow pain and joint swelling over the past two weeks that had now resolved. A mild transaminitis was also observed on admission labs with extremely elevated CRP and ESR. During the admission, his right knee began to hurt and XR revealed another small effusion. He subsequently developed a diffuse, maculopapular rash, which was thought to be a drug rash. He was switched from Zosyn to Ceftriaxone and then again to Clindamycin, but the rash, fevers, and leukocytosis persisted. Tests for gonorrhea, chlamydia, HIV, syphilis, and viral hepatitis were all negative. Fungal and anaerobic cultures of synovial fluid were negative.  Blood cultures did not show any growth and echocardiogram did not show any abnormalities or vegetation. ANA and anti-CCP were negative, and rheumatoid factor was only very weakly positive (only mildly above the upper limit of normal).

Finally, his ferritin came back at >17,000 and the diagnosis of Still’s disease was made. Still’s is a rare rheumatologic condition akin to juvenile rheumatoid arthritis. It is an out of control immune reaction that typically presents with daily or twice daily fevers, an evanescent salmon-colored maculopapular rash, and polyarticular arthritis. It can also cause severe nonsuppurative pharyngitis, liver dysfunction, pleural effusions, pericarditis, lymphadenopathy, and splenomegaly. The Yamaguchi criteria can be used to diagnose it after infectious, malignant, and other rheumatologic causes are ruled out. It is treated with high dose steroids and sometimes IL-1 or IL-6 inhibitors.

After this patient begun high dose steroids, his fevers and rash resolved, transaminitis slowly improved, and his arthritis became less severe, confirming the diagnosis of Still’s disease.

The Dutch Physician with a Calm Disposition

Today we reviewed a case of Boerhaave Syndrome, named after Dr. Hans Boerhaave who was the first physician to have written about a patient with an esophageal rupture after severe retching.

  • Suspect it in any patient with severe chest discomfort followed by vomiting or retching, [though it can happen without a history of retching]. The presence of subcutaneous emphysema on examination (crepitus) in conjunction with the aforementioned two makes Mackler’s Triad, which is seen in only 14% of patients.
  • The diagnosis is made by contrast esophagram (avoid Barium and chose Gastrografin instead) or by CT scan
  • Treatment is to make the patient strictly NPO, IV antibiotics and surgical consultation
  • Contrast this with a Mallory Weiss tear in which there is a partial thickness, longitudinal laceration of the esophagus or stomach that may present with chest pain, vomiting and hematemesis

We also reviewed the anatomically based framework to abdominal pain, and considered our differential for epigastric pain as well as severe, diffuse abdominal pain.

For epigastric pain, we considered the following:

  • Acute MI
  • Acute pancreatitis
  • Chronic pancreatitis
  • PUD
  • GERD
  • Gastritis
  • Gastroparesis
  • Functional Dyspepsia

For severe diffuse pain

  • obstruction (i.e SBO or hepatobiliary obstruction)
  • perforation (esophageal, gastric, or intestinal)
  • ischemia (ie mesenteric)
  • inflammatory/infectious

 

A Lung Mass… But what kind??

Our visiting Stanford resident, Dr. Tiffany Guo, presented a very interesting case of an elderly female with a heavy smoking history who presented with a subacute dry cough and progressive dyspnea on exertion with new unilateral shoulder pain.

An initial differential for any heavy smoker with a dry cough and dyspnea should be broad, but include the following tobacco-related diagnoses: COPD, lung cancer, pulmonary HTN, postobstructive pneumonia, and smoking-related ILD including Langerhans cell histiocytosis, respiratory-bronchiolitis associated ILD, desquamative interstitial pneumonia, and sometimes, IPF, acute eosinophilic pneumonia, and pulmonary alveolar proteinosis. The smoking-related ILDs are a heterogeneous group, but in general, they tend to be asymptomatic or present with dry cough and dyspnea, occasionally with systemic symptoms like weight loss and fever. Physical exam may show rales or clubbing and PFTs show a restrictive lung defect. The diagnosis becomes more clear with specific findings on HRCT scan. Although these disorders are rare, they are important considerations because some have treatments and patients may be eligible for lung transplantation.

With this patient’s new onset shoulder pain, we also discussed Pancoast syndrome as a possible diagnosis. Pancoast syndrome consists of shoulder pain (most common initial symptom), Horner syndrome (ipsilateral ptosis, miosis/pupilary constriction, and anhidrosis/loss of sweating on the face), and weakness of the muscles of then hand due to a superior pulmonary sulcus tumors. This was not the diagnosis in our particular patient, but is an important diagnostic thought.

Our patient’s chest X-ray revealed a right hilar mass in the lung. While waiting for biopsy and counseling your patient on your initial concerns for malignancy, it is helpful to have a basic knowledge of the main types of lung cancer and their treatments.

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Pericardial Effusion and Stable Cardiac Tamponade

Stable cardiac tamponade you say?? That’s right! Today, our esteemed Dr. Whitney Chew presented a fascinating case of a middle-aged woman with a remote history of malignancy who presented with a month of progressive fatigue, shortness of breath, and pleuritic chest pain, found to have a large pericardial effusion with compression of the right atrium and ventricle on echocardiogram concerning for cardiac tamponade. Vital signs were stable (BP 131/71 without tachycardia) and the patient was reported to be in no acute distress on documented physical exams.

Clinical Pearl: Cardiac tamponade can be acute OR subacute. When acute, the fluid accumulates quickly and the pericardium has no time to stretch or allow the body to compensate for the decreased diastolic filling. Hemodynamic collapse occurs quickly in this case. In subacute cardiac tamponade, usually from renal failure or malignancy, the fluid accumulates slowly, allowing the pericardial compliance to increase gradually. In this case, as much as 2L of fluid can accumulate in the pericardium before hemodynamic collapse occurs.

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CXR of pericardial effusion: Above are images of pericardial effusion on chest X-ray. On the left, cardiomegaly with a slight water bottle appearance can be appreciated. In addition, a retrocardiac air-fluid level with the air lower than the fluid despite the upright position of the patient is indicative of a pericardial effusion. The fluid is contained within the pericardium and sitting atop some aerated lung, creating this reverse air-fluid level. On the right, the later film shows the “Oreo Cookie Sign” of a vertical opaque line between 2 radiolucent vertical lines indicative of pericardial fluid between the pericardial and epicardial fat. With large pericardial effusions, widening of the subcarinal angle may also be seen.

A Gift for All You Budding Nephrons

Before I begin, I would like to thank Dr. Frank Luo and Dr. Amit Gohil for coming to today’s report and sharing with us their wisdom from years of clinical experience. I also would like to thank Dr. Jacobson for his continuous attendance and invaluable guidance at our reports. As Osler said, “the work of an institution in which there is no teaching is rarely first class” and we owe a debt of gratitude to all of our teachers for their service to us.

To proceed…esteemed colleagues: every once a while you get a case that pushes every aspect of your medical knowledge, diagnostic skills, and clinical reasoning — this was that case. Megan and Trevor presented a case of acute encephalopathy and hypothermia in a patient who ultimately was found to have the following:

  1. Lactic Acidosis
  2. Ketoacidosis
  3. Renal Failure
  4. Respiratory Acidosis
  5. Elevated Osmolar Gap

…among many many other derangements.

We first went through a focused differential of acute encephalopathy and hypothermia

  1. Sepsis
  2. Cardiogenic Shock
  3. Ingestions
  4. Adrenal Crisis
  5. Myxedemic Crisis
  6. Severe Hypoglycemia
  7. Neurologic Crises – brain mass, stroke
  8. Severe Trauma

We then learned that the patient was on Metformin and an SGLT-2 inhibitor and postulated the following sequence of events:

  • Empagliflozin is an SGLT-2 inhibitor known to cause euglycemic DKA, which may have been the etiology of his ketoacidosis. (on an unrelated note — remember that SGLT-2 inhibitors are known to increase the risk of genitourinary infections, particularly fungal infections)
  • The time course of renal failure is difficult to be certain of – but perhaps it was volume depletion from his SGLT-2 inhibitor (via an osmotic diuresis) that led to a pre-renal AKI
  • Metformin is known to cause a Type B lactic acidosis, which may have occurred in the setting of his AKI from above
  • Additionally, his HCO3 may have been so low, that he developed shock as a result of severe acidemia and subsequent type A lactic acidosis as well
  • His acidemia was so profound, that he could not fully compensate, leading to a respiratory acidosis
  • The combination of lactic acidosis, ketoacidosis and renal failure all could have contributed to his osmolar gap

Which leads us to a discussion of the osmolal gap. Checking the serum osms is useful in cases of ingestions, particularly when we suspect it could be a glycol or methanol. We calculate the osmolality based on readily available formulas, then compare it to the measured osmolality. If the measured is greater than the calculated by more than 10, you expect there are added extra osmoles in the blood. UpToDate has a fantastic way of approaching this:

  • With AGMA
    • Major causes of of a large osmolal gap
      • ethylene glycol
      • propylene glycol
      • methanol 
    • Causes of a smaller osmolal gap
      • ketoacidosis
      • lactic acidosis
      • severe CKD without regular dialysis
      • paraldehyde ingestion or injection
  • Without AGMA
    • ethanol
    • isopropanol
    • diethyl ether
    • infusion of mannitol, sorbitol or glycine
    • pseudohyponatremia (severe hyperlipidemia or hyperproteinemia)

Courtesy of UpToDate

Mucormycosis

Today, Dr. Trevor Rafferty presented an extremely interesting case of acute sinusitis in an uncontrolled diabetic that was rapidly progressive and progressed to include right facial edema, erythema, and numbness.

Management of acute sinusitis:

Acute sinusitis can be managed with supportive care in most cases as it is of viral etiology 98% of the time. Less than 2% are bacterial, with an extremely small percentage being of fungal etiology. If symptoms persist and/or worsen over 7-10 days or if the patient endorses a “double worsening” (symptoms getting better and then getting worse again), bacterial sinusitis should be suspected and antibiotics given. In immunocompromised hosts, antibiotics should be considered on a case by case basis and fungal sinusitis should always be on the differential diagnosis. In addition, one should always evaluate for signs of complications of sinusitis, which are orbital cellulitis, preseptal cellulitis, meningitis, abscesses, osteomyelitis, and infections of other adjacent structures. Worrisome signs and symptoms include nuchal rigidity, sepsis, proptosis, painful extraocular movements, diplopia, focal neurological deficit, eschar, and altered mental status.

Diagnosis of fungal sinusitis:

Diagnosis of fungal sinusitis is ONLY possible with a very high index of suspicion. It should be suspected in any and all patients with acute sinusitis in the setting of uncontrolled diabetes, organ transplant, chronic steroids, AIDS, IVDU, or other immunosuppressing medications or conditions. If the patient is in diabetic ketoacidosis or if there is clinical or imaging evidence of erosive disease, invasive fungal sinusitis must be ruled out surgically. Mucor especially thrives in patients with DKA due to an enzyme called ketone reductase, which causes it to thrive in environments rich in ketones. Mucor is angioinvasive and therefore, spreads quickly and produces eschar, necrosis, and frequently focal neurological deficits.

Endoscopic biopsies by ENT are the initial test of choice to obtain the histopathology and culture necessary to diagnosed fungal sinusitis, but are not very sensitive and if negative, do not rule out mucor. In most cases, more invasive exploration in the OR is necessary to look for necrotic tissue and eschar. B-D Glucan is not helpful in diagnosis as mucor does not have the cell wall components that make the test positive.

Treatment of mucormycosis:

The mainstay of treatment is surgical debridement, which often results in significant disfigurement. Multiple debridements are often necessary for source control. Antifungal treatment is also necessary and consists of amphotericin B initially and as a clinical responsive is observed, usually over several weeks, may be transitioned to posaconazole or isavuconazole. Mortality of sinus mucor is around 50%, pulmonary mucor 76%, and 96% for disseminated mucor. Antifungal treatment can be necessary for months and is usually continued until the period of immunosuppression can be stopped (if possible). For patients that cannot stop their immunosuppressing medications or diseases, they may required lifelong antifungal treatment. In addition to surgical debridement and antifungal therapy, aggressive treatment of predisoposing factors is necessary, including hyperglycemia, acidosis, and if possible, immunocompromise.