Ben Kitchens gave an excellent Resident Update Talk today on amyloidosis and its management. Check out the slides below and key points:
- Extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins
- Point mutations, deletions, and premature stop codons may result in structural changes predisposing to fibril formation
- Dr. Rudolph Virchow in 1854 first adopted the term “amyloid” to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine
- There are several forms of amyloidosis including AL, AA, dialysis-related, heritable, organ-specific
- AL amyloidosis is the most common in the U.S. and is caused by the deposition of monoclonal light chains, more often λ than κ
- Hepatic amyloid involvement has been reported in up to 90 percent of patients with AL amyloid
- Diagnosis requires characteristic findings on tissue biopsy and evidence that the amyloid deposits are composed of clonal light chains
- An abdominal fat pad aspirate or bone marrow biopsy may be positive in up to 80% of patients. If negative but suspicion remains high, then more invasive biopsy of clinically relevant tissue is needed
- Amyloid deposits consist of amorphous eosinophilic material that demonstrates apple-green birefringence when stained with Congo red and viewed under polarized light
- After a diagnosis is established, a cardiac assessment is critical, including electrocardiography and transthoracic echocardiography, which may show interventricular septal hypertrophy, restrictive physiology, and occasional “sparkling” changes in the myocardium
- Cardiac involvement is associated with poorer prognosis
- Treatment consists of melphalan and dexamethasone chemotherapy to eradicate the clonal plasma cells responsible for producing the pathogenic light chain. Autologous hematopoietic stem cell transplantation should be considered in younger patients without significant comorbidities
- Patients with poor performance status, major comorbidities, involvement of three or more organs, and advanced cardiac amyloidosis are not considered transplant candidates
- Bortezomib and lenalidomide regimens have also been used, particularly for relapsed disease
(Image from the Commonwealth Fund)
You’ve heard it before – the cost of healthcare is too high, and it keeps on rising! Some physicians tend to place responsibility for high medical costs more on “demanding patients” than themselves. However, new research in JAMA Oncology suggests otherwise, noting that patient “demands” directly account for a negligible change in physician behavior and thus expenditure. Take a look at the original article, or, for a more colorful read, the editorial “The Myth of the Demanding Patient.”
Dr. Theodora Ross, from the UTSW division of hematology and oncology, speaks about a new gene, beclin-1, that may be a target in treating triple-negative breast cancer. Her team expanded on work done by Dr. Beth Levine. Click the link to hear an NPR interview with Dr. Ross:
For more information, check out the original research.
- Eculizumab has shown greater efficacy than plasma therapy in the prevention and treatment of episodes of atypical haemolytic uraemic syndrome (aHUS)
- Eculizumab may be considered as a first-line therapy in children with a first episode of aHUS as it avoids the complications associated with apheresis and central venous catheters
- In adults, eculizumab can be used as a first-line therapy when aHUS diagnosis is undisputable, although plasma therapy should be used as a first-line therapy if uncertainty in diagnosis warrants further investigation
- Evidence of plasma resistance or dependence should lead to a prompt switch to eculizumab; the sooner eculizumab is initiated, the better the recovery of renal function
- Renal transplant candidates with a genetically determined risk of post-transplantation aHUS recurrence should be given a prophylactic protocol based on eculizumab if at high risk, and plasma exchange or eculizumab if at moderate risk
- Eculizumab may be effective in curbing part of the inflammatory process involved in a subset of C3 glomerulopathies
Nature Reviews Nephrology 8, 643-657 (November 2012) | doi:10.1038/nrneph.2012.214
Dr. Saad Khan, from the UTSW division of Hematology/Oncology, presented an update on the diagnosis and treatment of thyroid cancer. A point important for general internists is the evaluation of incidentally discovered thyroid nodules. The algorithm below may help clarify the diagnostic process:
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This morning on NPR, there was a interesting segment on how doctors deliver news to patients regarding prognosis of their cancer. At Memorial Sloak Kettering in NY, there are workshops for physicians on communication, particularly with delivering difficult news for patients. It’s part of an ongoing series by NPR on cancer. Click on the link below to check out the article and listen to the interview!
Cancer Patients And Doctors Struggle To Predict Survival
ITP is something we see with some frequency, but it can be tough to understand the pathogenesis, diagnosis and management of this dangerous condition. Take a look at this comprehensive quick reference guide by the American Society of Hematology for some help – it’s just 2 pages!
Dr. Rutherford gave us an excellent lecture about hemostasis disorders and therapy. Take a look at her lecture below (note, if you are an email follower, this post is visible only on the actual website – click the title above).
“The mark of a good ID clinician is not how many antibiotics he or she starts but how many he or she stops.” — Brad Cutrell
- “Classic” definition of FUO
- Fever > 38.3 C
- Duration > 3 weeks
- Unknown etiology after > 1 week hospital evaluation
- Revised Classification: proposed revisions decreased duration and removed inpt evaluation criteria
- Classic Definition: temperature higher than 38.0 °C (100.4 °F) for more than 3 weeks and either more than 3 days of hospital investigation or more than two outpatient visits without determination of the cause.
- Health care–associated FUO: temperature higher than 38.0 °C (100.4 °F) for more than 3 days in a hospitalized patient receiving acute care with infection not present or incubating on admission.
- Immune-deficient (neutropenic) FUO: temperature higher than 38.0 °C (100.4 °F) in a patient in with ANC < 500 in whom the diagnosis remains uncertain after more than 3 days despite appropriate investigation, including at least 48 hours’ incubation of microbiologic cultures.
- HIV-related FUO: temperature higher than 38.0 °C (100.4 °F) in a patient with confirmed HIV infection for more than 3 weeks in outpatients or more than 3 days in inpatients.
- Classic FUO etiologies fall into 5 major categories: Infection, Malignancy, Inflammatory, Miscellaneous, Unknown
- Distribution depends on decade, patient age, geography, and type of practice
- Tuberculosis (extrapulmonary, miliary, IC hosts)
- Occult abscess (abd/pelvic)
- Complicated UTI
- Culture-negative endocarditis
- Typhoid fever
- Visceral Leishmaniasis
- Lymphoma (esp. NHL)
- Renal Cell carcinoma
- Hepatocellular carcinoma or liver metastases
- Inflammatory Disorders
- Adult-onset Still’s Disease
- Temporal arteritis (Giant Cell arteritis)
- Polymyalgia rheumatica
- Drug Fever (abx, anti-seizure meds, NSAIDs, anti-arrhythmics)
- Alcoholic hepatitis
- Venous thromboembolic disease
- Endocrine disease (hyperT, adrenal insufficiency, pheo)
- Disordered heat homeostasis (“central fever”)
- Factitious Fever (Munchausen)
- Special Populations
- Infectious most often, particularly viral and respiratory
- CTD: Kawasaki in younger, AOSD in older children
- CTD (GCA and PMR) and malignancy more common than in < 65 age group
- Returning Traveler
- Malaria, typhoid fever, amebic liver abscess, acute HIV
- History and Physical!
- Recent prospective Dutch series found average of 10.5 potential diagnostic clues per pt from history/exam and only 3 per pt from lab testing (81% misleading)
- Laboratory Testing
- Best guided by history/exam clues, not “shotgun” approach
- Laboratory testing yields diagnosis in 25% of cases
- CXR and CT abdomen/pelvis part of initial tests
- MRI/MRA good for CNS, spine, and vasculitis evaluation
- Older nuclear tagged scans and Gallium scans have been largely replaced by FDG-PET scans
- Recent meta-analysis showed pooled sens. 98% and spec. 86% for FDG-PET, arguing for role if initial w/u negative
- Invasive Testing
- BM evaluation useful, especially if abnormal CBC or immunocompromised host
- Biopsy of sites with suspected involvement in select cases
Management and Prognosis
- Therapeutic trials of abx generally not recommended
- “Non-specific Rx rarely cures FUO but may delay Dx.”
- Exceptions: empiric steroids for suspected GCA or empiric abx in neutropenic patients
- Depends on age and etiology of FUO (worse with elderly and malignancy as etiology)
- Most without Dx after extensive evaluation have good prognosis with low mortality and fever resolution
- Remember: The cause is more likely a common diagnosis presenting in an atypical fashion than a rare disease presenting in a typical fashion.
Great lecture today by Dr. Courtney from the Division of Heme/Onc at UT Southwestern. Check out the slides below!