A word on blood films:

Iron deficient Anemia:
On the blood film you would expect hypochromic micorcytosis, pencil forms, target cells

Multiple Myeloma:

characterized by proliferation of the plasma cell producing a monoclonal immunoglobulin
blood film may demonstrate rouleaux (stacked coins)

Diagnosis: must meet 3 criteria

• monoclonal spike (M-protein) in serum or urine (although 30g/L often quoted that quantity is not met in >40% of patients and 3% of multiple myeloma is actually ‘non-seretory’


• >10% clonal bone marrow plasma cells


• presence of tissue or organ consequences “CRAB” – hyperCalcemia, Renal failure, Anemia and/ or lytic Bone lesions.

Unanswered Question of neurological symtpoms in multiple myeloma…..hyperviscosity is a syndrome of increased blood viscosity classically caused by immunoglobulins leading to impairment of the microcirculation with CNS effects including somnolence, headache, vertigo, nystagmus, hearing loss, visual impairment. Although generally described in assocaition with the IgM paraprotein of Waldenstroms, it has been reported in multiple myeloma (when abn monomers ig IgG, IgA or kappa light chains are produced.

Altered sensorium is an indication for immediate plasma exchange. In general you would like to demonstrate a high vicosisty prior to acting to differentiate the neruological changes from those of CNS myeloma etc...

The appearance of the CXR in various point of TB infection is important information....what are we looking at here????

Some terminology....

Ghon focus: granuloma in the lung

Ghon complex: graulmoa and ipsilaterl adenopathy

Post Primary TB: nodular / alveolar infiltrates in the upper lung zones (apical and posterior segment of the upper lobe and superior segment of the lower lobe), potentially cavitation


Atypical Patterns:

• Lower and mid lung zone infiltrates: in isolation or in association +/- pleural effusion
• Pleural effusion: usually unilateral, almost always exudative, high percentage of lymphocyte count
• Miliary TB: 1-5mm discrete nodules scattered throughout the lung
• Tuberculmoa: solitary lesion of the chest x -ray

Neuroleptic Malignant Syndrome
An idiosyncratic, potenitally fatal cmplication of treatment with antipsychotics.

Pneumonic: FARM
F – fever
A – autonomic dysfunction
R – rigidity
M – mental status changes
( may progress to rhabdomyolyis +/- ARF)

Culprit Drugs:

• antipsychotics (typical > atypicals)
• dopamine antagonists (metoclopramide, proclorperazine)
• withdrawal of dopaminergics
• muscle relaxants

Clinical Course:

• most cases develop within 30 days of initiating therapies
• progression is insidious over days
• mental status changes usually precede systemic signs
• resolves 7-10 days after discontinuation of culprit drug
  

Treatment:

• discontinue culprit medication
• supportive care (fluids, cooling)
• watch for rhabdomyolyis and consider bicarb drip
• possible medications to consider – benzodiazepines, dopaminergic agents, dantrolene
• caution in restarting antipsychotics once resolved
• get some help from psyc!

for more details se review article....

http://ajp.psychiatryonline.org/cgi/reprint/164/6/870
Am J Psychiatry 164:6, June 2007

Where did all the staph go......

Differential for Acute Monoarthritis:

Infectious: SEPTIC UNTIL PROVEN OTHERWISE!!! (Gonococcal vs Non-gonococcal)
Crystal Arthropathy: Gout, Pseudogout (CPPD), Hydroxyapatite
Inflammatory
Seropositive arthritis (early RA or SLE)
Seronegative arthritis (psoriatic, Ankylosing spondilitis, IBD, reactive)
Degenerative: OA

Trauma:Hemarthrosis

Extra-articular: Bursitis, cellulites, ruptured Baker’s cyst, tendonitis, etc…

Check out this link to a recent CMAJ review with an approach to monoarthitis:
http://www.cmaj.ca/cgi/content/full/180/1/59

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On another note.....we also talked a little bit about osteomyelitis. On an x-ray you might se:

• Findings: Early
  Soft tissue swelling
  Periosteal reaction (Subperiosteal elevation)


• Findings: Later
  Osteolysis
  Sequestra (islands of necrotic bone)
  Bone abscess (Brodie's abscess)
  

Efficacy: Test sensitivity 62% (43-75% in DM Foot Osteo), Test Specificity 64% (65-83% in DM Foot Osteo)
Limitations: Bone changes lag infection by 10-20 days, XRay changes not seen until 40-70% bone resorbed

Going back to the clinical exam this article looks at predictive findings for osteomyelitis in diabetics while you wait for that MRI....

http://jama.ama-assn.org/cgi/content/full/299/7/806

My feet are burning.....

When a patient presents with fever and headache one always worries about meningitis. Here us a quick overview of the basics provided by the facilitator.

In addition to the differential of fever and headache including meningitis, another consideration in the appropriate clinical scenario may be seroconversion of HIV. Fever is a common presenting complaint. Headaches can also accompany acute illness and tends to be described as retro-orbital pain exacerbated by eye movement.

SEROCONVERSION ILLNESS:
The symptoms of acute primary HIV infection are non-specific and often resemble those of other viral illness such as mononucleosis. The most frequent symptoms include fever, lymphadenopathy, sore throat, mucocutaneous lesions, myalgias / arthralgias, diarrhea, nausea vomiting, weight loss and headache. Although it is challenging to discern the frequency of the syndrome vs. subclinical acute infections, many people feel this syndrome is under recognised and occurs in approaching 90% of patients.
The acute illness occurs generally within 2-4 weeks of infection although has been documents up to 10 months after exposure. The symptoms described come on rapidly to their most severe within about 24-48 hours. They are self-resolving within 2 weeks although general fatigue may continue for months.
Lab findings: Initially leukocytes fall. Eventually lymphocyte recovery is seen with CD8> that CD4 resulting in the ratio (CD4:CD8) less than 1.0. Other findings include hepatitis and thrombocytopenia.
Clinical Implications: Patients with severe acute illness are felt to have high infectivity and have a worse long term prognosis in terms of rate of progression of their disease. More recently, evidence for initiation of treatment during the acute illness is mounting.


Of final note… during the acute illness HIV antibody testing may be used to make the diagnosis. If is falsely negative due to lack of seroconversion an HIV RNA may be used in suggestive cases. A CD4 count is occasionally used as a surrogate but there is a differential associated with a low CD4 count so it is far from a diagnostic test. Please see article: Current Opinion in Rheumatology 2006;18:389-95

Bullous Skin Disease

Steven Wasnt In Morning Report....

Young person presents with platelets of 4......

Differential Diagnosis of Thrombocytopenia

Decreased Platelet Production
•Marrow: fibrosis, aplasia/dysplasia (Fanconi’s), infiltration
•Cytotoxic agents / radiation
•Viral: HIV, EBV, parvo, mumps
•Other infection: infectious infiltration of marrow
•ETOH
•Vitamin deficiency: B12, folate

Accelerated Destruction:
•microangiopathic disease: TTP/HUS, DIC, HELLP, PET, malignant hypertension
•Vasculitis
•Prosthetic heart valves
•Other mechanical: IABP, hemangiomas
•Infection: malaria
•Immune:
•autoimmune – ITP
•allo immune – post transfusion purpura
•secondary: SLE, APLA, CLL drugs (heparin, quinidine, etc), HIV

Distribution / Dilutional
•Splenic sequestration
•Pregnancy

Pseudothrombocytopenia

Idiopathic Immune Thrombocytopenia Purpura

The diagonsis of ITP is a diagnosis of exclusion after consideration / work up of other enities listed in the differential. A bone marrow biopsy may or may not be part of your work up but is not considered necessary in all patients. Criteria which should prompt bone marrow biopsy include:
•Age >60
•Other cytopenias
•Poor response to treatment
•Significant splenomegaly

First line treatment of acute ITP is steroids. Please see NEJM review for more details. http://content.nejm.org/cgi/reprint/346/13/995.pdf

More recently another treatment strategy has been proposed with high dose, short course steroids (dexamethasone). Check out this article in Blood which is the most recent of 2 trials that test this strategy: Blood. 2007 Feb 15;109(4):1401-7. Epub 2006 Oct 31.

Have a Heart.....

Heart failure can be defined as a clinical syndrome characterized by impaired ventricular function and elevated diastolic filling pressures which result in decreased exercise tolerance. The approach to heart failure involves diagnosis of the underlying cause of the heart failure as well as identification of the acute precipitant of the presentation. Today in morning report we had a more unique opportunity to discuss the etiology of heart failure as a new presentation.

We made the diagnosis initially based on symptoms of heart failure which include (but are not limited to):

• dyspnea
• paroxysmal nocturnal dyspnea
• orthopnea
• increasing peripheral edema (or ascites / weight)
• abdominal pain (RUQ)

Physical Exam supported the diagnosis by findings of:

• tachycardia
• hypoxia and respiratory distress
• postural respiratory distress
• distended neck veins
• elevated JVP
• S3, S4
• peripheral edema, ascites

Chest X-ray findings will also support the diagnosis with findings including:

• cardiomegaly
• cephalization of blood vessels (vascular redistribution)
• interstitial pattern of increased opacity with Kerley B lines
• bilateral hilar 'cloudiness' with a butterfly or batwing appearance due to alveolar edema
• peribronchial cuffing
• pleural effusions (right>left)

Finally, we discussed on approach to etiology of heart failure which includes primary vs secondary causes. Primary causes of heart failure are defined anatomically as problems with the valves, pericardium, myocardium, blood vessels and the electrical systems.

How high is too high????

What would you do when someone presents with an elevation in serum cortisol. The diagram beside shows some of the clinical features they may demonstrate...

• mood / sleep alterations
• acne
• moon faces
• dorsal fat pad
• cardiac hypertrophy / HTN
• central obesity
• abdominal striae
• osteoporosis
• muscle wasting / weakness
• easy bruising
• thin skin
• ulcerations and poor healing

CONFIRMING THE DIAGNOSIS

Thanks to the facilitator we discussed the limitations of isolated serum cortisol measurements including the diurnal variation of the hormone. We discussed the work-up for ? Cushing syndrome including available tests.

Urine 24 hour free cortisol: 85% + sensitive with false positives including over-collection, increased urine output and some drugs (carbemazepine and fenofibrinate). False negatives include incomplete collection or subclinical disease.

Dexamethasone 1mg supression test: 95% sensitive. False negatives of this test include estrogen treatment, drugs affecting dex metabolism (barbituates, dilantin, tegretol, rifampin) and acute or chronic illness.

Late Night Salivary Cortisol: 93% sensitive and 100% specific but not well studied

CONFIRMING THE ORIGIN (ACTH mediated?)

Once the diagnosis has been confirmed...the next step is to look at tests which help to determine the etiology of the excess cortisol state. In a broad sense (and ignoring exogenous sources) this differential includes:

ACTH excess (pituitary, ectopic ACTH and ectopic CRH) - THE MAJORITY approx80%)

ACTH suppressed (adrenal adenoma, adrenal hyperplasia, adrenal carcinoma)

This next step is easily determined by measuring the serum ACTH.

AND NOW WHAT.....

If the ACTH is suppressed - easy...look at the adrenals (CT scan)

If the ACTH is elevated you then must go on to decide whether this is pituitary-derived ACTH, ectopic ACTH or ectopic CRH production. Classically the test described for this differentiation is the High Dose (8mg) Dexamethasone Suppresion Test. This is said to be helpful because 'only' pituitary ACTH will have a positive suppression test (i.e. measured am cortisol is low after 8mg dexamethasone given the night before). The reality is that only 60-80% of pituitary ACTH excess will have a positive suppression test (cortisol suppressed) and 30% of ectopic ACTH producing states will have a positive suppression test....so you see far from perfect.

Other tests to add to your repertoire include:

• CRH stimulation test
• Vasopressin stimulation test
• Petrosal Venous Sinus Sampling
• Imaging (MRI brain and CT other....)

For complete details see "Evaluation and treatment of Cushing's syndrome" The American Journal of Medicine Vol: 118, Issue: 12, December, 2005 article. Direct LINK:

http://scholarsportal.info/cgi-bin/sciserv.pl?collection=journals&journal=00029343&issue=v118i0012&article=1340_eatocs