GI Kaposi Sarcoma – 8/20/18

Thanks to Wendy for presenting a case of an elderly man with h/o remote renal transplant presenting with chronic progressive DOE, lower extremity edema, and upper and lower GI bleed, found to have AIDS-related GI kaposi sarcoma and associated protein-losing enteropathy!


Clinical Pearls:

  • Keep a broad differential for patients on immunosuppression
  • Incidence of KS is higher with CD4 counts <200 but it can be seen in CD4>500 as well.
  • Prognosis is generally good with treatment.  Poorer prognosis is associated with visceral involvement (as opposed to cutaneous), multiple opportunistic infections, and CD4<200
  • Mainstay of therapy is anti-retrovirals.  Chemotherapy can be used for ARV unresponsive disease, significant edema, extensive organ involvement, or IRIS.  Studies on chemo + ARV vs ARV alone showed no survival benefit with the former.
  • Thanks to Dr. Szumowski for the clinical pearl on use of sirolimus in renal transplant recipients with KS (article here).

Differential for odynophagia:

  • Infectious
    • HSV
    • CMV
    • Fungal
      • Candida ⇒ risk factors include dentures, immunosuppression (AIDS, chemo), radiation to head and neck, recent antibiotics
      • Others: crypto, histo, blasto, aspergillus
    • Mycobacteria
  • Medication-induced
  • Less common
    • Reflux esophagitis
    • Crohn’s

Kaposi Sarcoma:

  • Vascular tumor associated with HHV-8
  • Four different epidemiologic forms:
    1. AIDS-related: most common type in US
      • Higher incidence with CD4 <200 but can be seen with CD4 >500 as well.
    2. Endemic/African
    3. Organ transplant-associated (higher incidence after solid organ transplant)
    4. Classic (indolent cutaneous proliferative disease in older men of Mediterranean or Jewish descent)

KS in the GI tract:

  • Can occur in the absence of cutaneous disease
  • Symptoms range from asymptomatic to weight loss, abdominal pain, n/v, UGIB/LGIB, malabsorption, diarrhea
  • Inflammatory cytokine syndrome:
    • Systemic inflammation in AIDS-related KS
    • Symptoms:
      • Fever
      • Edema
      • Neuropathy
      • GI/respiratory symptoms
      • Hypoalbuminemia (can occur in the absence of the who syndrome)
        • Secondary to protein losing enteropathy (check stool clearance of alpha-1 antitrypsin)
      • Thrombocytopenia
      • Splenomegaly
Staging of KS: 
  • Extent of tumor (T): limited to skin with minimal oral cavity involvement is good.  Visceral involvement has poor prognosis.
  • Immune status (I): Degree of immunosuppression from HIV. CD4 <200 has worse prognosis
  • Severity of systemic illness (S): poor prognosis a/w h/o OI, thrush, B symptoms, etc.
  • Endoscopy and bronchoscopy are only done if initial stool test and CXR are abnormal
Treatment:
  • Goal: palliation, prevention of disease progression, and shrinkage of tumor to alleviate edema, organ compromise, and psychological distress
  • Systemic
    • Treatment with potent ART
      • IRIS can occur within 3-6 weeks of initiation
    • Chemo: for patients with advanced KS and rapid progression
      • Indications
        • >25 lesions
        • Unresponsive to local treatment or ART alone
        • Extensive edema
        • Symptomatic visceral involvement
        • IRIS
      • Agents:
        • Pegylated liposomal doxorubicin or daunorubicin
        • Paclitaxel, bleo, vinblastine, vincristine, etoposide
    • Chemo + ART or ART alone? While response rates are higher with the former, no survival benefit
  • Local symptomatic therapy
    • Intralesional chemo (vinblastine)
    • Radiation therapy
    • Topical alitretinoin

 

CML, leukocytosis, and leukostasis – 8/14/18

Yours truly presented a case of a middle aged man admitted for traumatic rib fracture overnight and found to have a WBC of 368k with cytogenetics consistent with CML!


Clinical Pearls

  • WBC > 100k is most consistent with leukemia.
  • WBC up to 75k can be seen with C diff infection.
  • Leukostasis is most commonly associated with AML > ALL > CML > CLL and defined as hyperleukocytosis with evidence of end-organ damage (CNS, renal, pulm)
    • Hematologic emergency!
    • Treatment is three-fold:
      • cytoreduction: leukapharesis, hydroxyurea, TKI (especially for CML), induction chemo (with other malignancies)
      • FLUIDS
      • prevention of tumor lysis syndrome (another heme emergency): allopurinol, FLUIDS

Differential for leukocytosis:

Blood Cell Lineage

  • Neutrophilia (most common, >7000/mm^3)
    • Infections
    • Stress/trauma
    • Chronic inflammation
    • Meds
    • Leukemias
  • Lymphocytosis (>4500/mm^3)
    • Pertussis
    • Syphilis
    • Viral infections
    • Hypersensitivity reactions
    • Leukemias/lymphomas
  • Monocytosis (>880/mm^3)
      • EBV
      • TB
      • Fungal disease
      • Autoimmune disease
      • Splenectomy
      • Protozoan/rickettsial infections
      • Leukemias

     

  • Eosinophilia (>500/mm^3):
    • Neoplasm
    • Adrenal insufficiency
    • Asthma/atopy
    • Collagen vascular disease
    • Parasites

CML:

  • Refer to this and this prior posts on the blog for all the details!
  • Some details to highlight
    • Smear tends to show lots of immature myeloid cells from many different stages of maturation (some blasts, metamyelocytes, myelocytes, bands, and mature neutrophils)
    • If >20% blasts, then think AML

Leukostasis:

  • Defined as symptomatic hyperleukocytosis and is a hematologic emergency!
  • Mortality rate is can be as high as 40% within the first week of presentation.
  • Clinical manifestations of ischemia primarily in CNS, lungs, and kidneys.  Can also see limb ischemia and priapism.
  • Malignancies at highest risk of leukostasis in order of prevalence:
    • AML (WBC >50k)
    • ALL (WBC >100k, though tends to present with TLS and DIC much more commonly than leukostasis)
    • CML (WBC >100k)
    • CLL (WBC >400k)
  • Treatment:
    • FLUIDS, lots and lots of fluids
    • Cytoreduction: lowers the WBC
      • Leukapharesis: not readily available as it requires a dialysis line and trained nursing staff
      • Hydroxyurea: to lower the WBC
      • Tyrosine kinase inhibitors (especially for CML related leukostasis)
      • Induction chemo (for non-CML related leukostasis)
    • Prevent tumor lysis syndrome:
      • FLUIDS
      • Allopurinol
    • In hemodynamically stable patients AVOID TRANSFUSION – it’s like adding fuel to the fire and can worsen ischemia.

Catastrophic Antiphospholipid Syndrome, +/- Heparin induced thrombocytopenia & thrombosis, +/- SLE 8/1/2018

Wendy presented a fascinating (and confusing!) case of a patient with history of APS and DVT/PE on chronic warfarin presenting with painful, non-blanching, palpable purpuric rash on the left thigh and lower abdomen found to have thrombocytopenia,  and proteinuria. Skin biopsy revealed small vessel microthrombi. Work up positive SRA, positive ANA, positive DsDNA, low complements… Base on this presentation, the patient possibly has catastrophic antiphospholipid syndrome, with heparin induced thrombocytopenia, and newly diagnosed SLE!

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Cholangiocarcinoma – 7/11/18

Eric presented the case of an elderly woman with no known medical history presenting with subacute onset of painless jaundice and liver failure, found to have perihilar cholangiocarcinoma.


Clinical Pearls:

  • Cholangiocarcinomas are the second most common primary malignancy of the liver after HCC.
  • Perihilar disease is most common.  Can also present with intrahepatic or distal duct involvement.
  • Risk factors include Primary Sclerosing Cholangitis, parasites, and biliary cysts.
  • Metastases occur early in the disease course with the liver being the most common site.
  • Treatment
    • Distal cholangiocarcinoma has the highest resectability.
    • Surgery is the only cure but only a minority of patients present early enough

Capture

Cholangiocarcinoma:

  • Second most common primary malignancy of liver after HCC
  • Can be intrahepatic, perihilar (most common), or distal
  • Risk factors include:
    • PSC
    • Parasitic infections (liver flukes: clonorchis and Opisthorchis)
    • Biliary atresia
    • Biliary cysts
    • Cholelithiasis, cholecystitis, and hepatolithiasis
  • Mets occur early in disease course except for distal disease
    • Perihilar disease: liver is the most common site of met
    • Intrahepatic: peritoneum, lungs, pleura
    • Distal cholangiocarcinoma: liver, lungs, peritoneum
  • Treatment:
    • Distal disease has the highest resectability
    • Surgery is the only cure but only a minority of patients present early enough
    • Liver transplant in an option for those with
      • perihilar disease
      • < 3 cm tumor size
      • No extrahepatic spread
      • No percutaneous biopsy (increases risk of hematogenous spread)

 

B12 deficiency induced hemolytic anemia – 6/27/18

Ernest presented an interesting case of a middle aged man with h/o CVA presenting with symptomatic megaloblastic anemia, found to have vitamin B12 deficiency induced thrombotic microangiopathy!


Clinical Pearls:

  • A “pseudo” TMA can develop in patients with severe vitamin B12 deficiency via red cell destruction in the bone marrow, leading to high LDH but modest rise in total bilirubin.
  • B12 related hemolysis is similar to TTP so the latter must be ruled out!
  • Treatment involves aggressive vitamin B12 replacement and is not responsive to plasmapharesis.

Differential for megaloblastic (MCV >120) anemia:

  • Vitamin B12 deficiency (elevation of both MMA and homocysteine)
  • Folate deficiency (elevation of homocysteine alone)
  • Drug induced (methotrexate, hydroxyurea, zidovudine, azathioprine, 5-FU, acyclovir, capecitabine)
  • Copper deficiency

When schistocytes are on the smear –> non-immune hemolysis.

Primary TMA syndromes:

  • TTP
    • Low levels of ADAMTS13
    • Renal failure, neurologic changes, fever, schistocytes, thrombocytopenia
      • Classic pentad only seen in 1/3 of patients
      • Triad of elevated LDH, schistos, and thrombocytopenia? –> check ADAMTS13
  • Shiga toxin mediated HUS
    • Shigella and certain serotypes of E Coli such as O157:H7 and O104:H4.
    • Classically with renal dysfunction and HTN as predominant findings
    • Bloody diarrhea
    • More common in children
  • Complement mediated
    • Hereditary deficiency of regulatory proteins in the alternative complement pathway
  • Drug mediated
    • Quinine, quetiapine, immunosuppressants, chemotherapy, calcineurin inhibitors
  • Metabolism mediated
    • Cobalamin C deficiency (inborn error of metabolism)
      • Mutations in the MMACHC gene (methylmalonic aciduria and homocystinuria type C)
  • Coagulation mediated
    • Hereditary deficiency of proteins in the coag pathway

Systemic disorder associated with MAHA and thrombocytopenia:

  • Pregnancy complications (HELLP)
  • Severe HTN
  • Systemic infections (bacterial endocarditis, HIV, CMV, RMSF)
  • Malignancies (with or without DIC)
  • Autoimmune diseases: SLE, systemic scleroderma, APLS.
  • DIC
  • Severe vitamin B12 deficiency

Final note on pernicious anemia:

  • Most common in Nothern Europeans
  • Check in people with vitamin B12 deficiency and no other identifiable cause
  • Intrinsic factor antibodies are the test of choice
    • Low sensitivity but high specificity
    • High sensitivity but low specificity (seen in other autoimmune disease as well as healthy individuals without autoimmune disease)
  • What about Schilling test?
    • Not available anymore!

References:

Acharya et al. Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case reports and review of the literature. J Hematol Oncol. 2008.