8/9/17 Resident Morning Report – Dyspnea on Exertion, Fatigue, Conjunctival Pallor, Splenomegaly, B12 deficiency, Pernicious Anemia

CC: Dyspnea on exertion

ID: 42 yo male with no past medical history presents with dyspnea on exertion and fatigue for 3 weeks. He becomes short of breath with walking ½ block when his baseline was walking miles.  He has no chest pain, paroxysmal nocturnal dyspnea, lower extremity edema, cough, or orthopnea. In addition he reports unintentional weight loss of 10 lbs over 3 months, low appetite, and night sweats. Social history is pertinent for drinking six 24 oz beers per day.  His exam is notable for conjunctival pallor and hepatosplenomegaly.  See the following notable labs:

LDH >5000

Haptoglobin <20

Retic 2.5%

Overall picture is consistent with ineffective erythropoiesis.  The peripheral smear demonstrates macrocytic red blood cells and hypersegmented PMNs, narrowing the diagnosis to folate and/or B12 deficiency.  His B12 returned as <100 and Homocysteine/MMA elevated confirming that patient had significant B12 deficiency leading to his pancytopenia.  IF-Ab and Parietal Cell Ab were positive which made Pernicious Anemia the most likely cause given lack of other malabsorptive conditions, though patient likely had poor nutrition from his alcohol use complicating the picture. 

Morning Report Pearls:

Pancytopenia is a broad differential including infection (EBV, CMV, HIV, Cocci, Histo, TB), rheumatologic conditions (RA, SLE, Sarcoid), drugs, nutritional deficiencies (B12, folate and copper), Zinc toxicity, Lymphomas/Leukemias, Myeloproliferative disorders like MDS and Myelofibrosis, Aplastic Anemia, Liver disease, Alcohol toxicity, Amyloidosis, HLH, Metastatic cancer – see prior Morning Report Post from 5/19/17

Macrocytosis is classically seen in a few of these causes: B12/folate deficiency, MDS, Alcohol toxicity, and Liver disease

Peripheral smear is your friend and can cinch the diagnosis when you see hypersegmented PMNs like in this case of B12 deficiency

Once the diagnosis of B12 deficiency is made, you need to think of causes: malabsorption (due to IBD, celiacs, tropical sprue, gastric bypass), medications (PPI, metformin), pernicious anemia, malnutrition

If patient not responding to B12 supplementation, consider pursuing a diagnosis of MDS with bone marrow biopsy. Indirect bilirubinemia and the elevated LDH should improve within 1-2 weeks following B12 treatment but cell counts can take months to normalize.

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)


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)