5/19/17 Intern Morning Report – Fevers, Fatigue, Hepatosplenomegaly, HLH

CC: fevers, malaise, mild shortness of breath

ID: 40 yo female with no medical history presents for 1 week of fevers, malaise, and mild shortness of breath.  She also notes a 1 year history of intermittent fevers, fatigue, chills, night sweats, weight loss, and LUQ abdominal fullness.  On exam, she was noted to be febrile to 39.3 with diffuse lymphadenopathy and splenomegaly.  She was found to be pancytopenic on presentation with WBC of 1.3, Hgb of 6.5, and Plt of 79.  Further workup revealed a ferritin of 2,757, LDH of 617, and triglycerides of 251.  Autoimmune labs were negative and a CT scan demonstrated splenomegaly with multiple enhancing lymph nodes throughout.  A bone marrow biopsy demonstrated histiocytes comprising 50% of the bone marrow and the patient was diagnosed with hemophagocytic lymphohistiocytosis.

Don’t forget:

  • To meet the criteria for HLH, the patient must have the right clinical picture and 5 of the following:
    • fever > 38.5C
    • splenomegaly
    • cytopenias (at least bicytopenia with Hgb < 9, Plt < 100, or ANC < 10000)
    • hypertriglyceridemia (fasting trigs > 265) and/or hyperfibrinogenemia (fibrinogen < 150)
    • hemophagocytosis in bone marrow, spleen, lymph node, or liver
    • low or absent NK cell activity
    • ferritin > 500 ng/ML
    • elevated soluble CD25

Pearls from morning report:

  • To examine for splenomegaly, start palpation in RLQ as the spleen enlarges towards that direction.
  • The combination of pancytopenia and constitutional symptoms should lead to workup for infection (viral illness, miliary TB, fungal infections, endocarditis), HLH, hematologic malignancy, or autoimmune disease.
  • When ferritin levels are significantly elevated (in the high hundreds to thousands), causes that should come to mind include: Still’s Disease, HLH, disseminated histoplasmosis, hemochromatosis, and liver failure.
  • The workup of HLH is not complete after its diagnosis – you must evaluate for underlying precipitants/causes of HLH.

Random trivia:

HLH was first described in 1939, but more fully understood in 1952 when two siblings in a family passed away from HLH (and another sibling 6 years later).


Want to read more?

Hemophagocytic lymphohistiocytosis: review of etiologies and management (J Blood Med)


References: 

Weinzierl KP, Arber DA. The Differential Diagnosis and Bone Marrow Evaluation of New-Onset Pancytopenia. Am J Clin Pathol. 2013;139:9-29.

Berliner N, Gansner JM, Schrier SL, Rosmarin AG. Approach to the adult with unexplained pancytopenia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on May 19, 2017)

1/20/17 Intern Morning Report – Tumor Lysis Syndrome, Metastatic Melanoma

CC: Masses, back pain, fatigue

ID: 58 yo incarcerated man with HTN and history of smoking/IVDU presents with soft tissue masses on his back and legs starting 3 months ago. He started to feel low back pain at this time, along with significant fatigue. Other symptoms include weight loss over the past 8 months and intermittent fevers the past 3 weeks. Exam was notable for firm masses on his R back, R buttock, and L inner thigh as well as bilateral pitting edema. BMP on admission was notable for hyperkalemia, hyperphosphatemia, anion gap metabolic acidosis and renal failure; additional labs ordered showed a uric acid level of 13.6 mg/dL and LDH >5000 U/L. MRI Lumbar spine showed enlarged bilateral paraspinal muscles with possible underlying mass and hematomas. CT images showed revealed extensive metastatic involvement of skeletal muscles and thoracic/retroperitoneal lymph nodes. The patient underwent an ultrasound-guided biopsy of the back mass; pathology revealed malignant melanoma. He was also diagnosed with tumor lysis syndrome (prior to any chemotherapy administration) and was started on IV fluids, allopurinol, and rasburicase.

metastatic-melanoma
CT Abdomen/Pelvis: Extensive metastatic involvement of skeletal muscles and thoracic/retroperitoneal lymph nodes.

Pearls from morning report:

  • Allopurinol alone is insufficient to treat hyperuricemia since its action is in decreasing uric acid formation – use rasburicase for preexisting hyperuricemia.
  • Be aggressive about IVF hydration!  See the Pearls from 11/4/16 morning report for indications for renal replacement therapy in TLS.
  • Spontaneous tumor lysis syndrome is rare, but is usually seen in Non-Hodgkin’s Lymphoma and acute leukemia.

Random trivia:

President Jimmy Carter was diagnosed with metastatic melanoma to the liver and brain.  He received immunotherapy with pembrolizumab and now reports he is now cancer free!


Want to read more?

How I treat hematologic emergencies in adults with acute leukemia (Blood)
Tumor lysis syndrome (New England Journal of Medicine)


References: 

Howard SC, Jones DP, Pui CH. Tumor Lysis Syndrome. N Engl J Med. 2011;364(19):1844-54.

11/9/16 Resident Morning Report – Hemarthrosis, Acquired Factor VIII Inhibitor

CC: 2 days of L knee pain and swelling

ID: 58 yo homeless male with alcohol abuse and seizure disorder presents with 2 days of L knee pain and swelling.  He reports a history of frequent falls (while intoxicated) and increased joint swelling after these falls over the past 4-5 months.  Exam was notable for diffuse L knee swelling, full ROM, stable varus/valgus maneuvers, negative posterior drawer test with improvement in pain with passive motion.  Joint fluid analysis demonstrated markedly bloody red fluid with 1,333 nucleated cells, 25% neutrophils, 40% lymphocytes, 29% monocytes, and 6% eosinophils.  Labs were notable for Hgb of 8.8, Plts of 384, and PTT of 84 secs which did not correct on mixing study – subsequent workup with a Factor VIII inhibitor assay was remarkable at 760 Bethesda Units.  Patient was ultimately found to have a renal cell carcinoma (RCC) and diagnosed with hemarthrosis likely secondary to acquired Factor VIII inhibitor from his underlying RCC.

synovial-joint-fluid-analysis

Joint Fluid Analysis (PDF)

 


Pearls from morning report:

  • Causes of bloody joint effusions include: hemophilia, trauma, malignancy, Charcot joint, and arteriovenous malformations.
  • Causes of acquired factor inhibitors include: pregnancy, malignancy, drugs,

Random trivia:

The lupus anticoagulant antibody was identified by our very own Dr. Donald Feinstein in 1972.  Dr. Feinstein continues to round with our hematology consult service here at LAC+USC!


Want to read more?

Acquired haemophilia: an overview for clinical practice (European Journal of Haematology)
How I manage patients with acquired haemophilia A (British Journal of Haematology)


References: 

Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician. 2003;68(1):83-90.