UT Houston Morning Report

April 20th - MHH - Fever in the MICU

2010-04-26T07:48:00.000-07:00

At morning report a case was presented of a patient that developed mucormycosis after being in the ICU.

Here is a general overview/approach to patients that fever either in the MICU, or after being transferred out of the MICU. This may be hard to piece out, as some studies have suggested that approximately 70% of MICU admissions have a documented fever on admission, and 55%-90% of those admitted without a fever develop one sometime during their MICU stay.

Why is this important? Well, besides finding a cause - mortality seems to be affected. Studies disagree - some say that "any fever" increases mortality, and others state that only prolonged fever increases mortality. Nonetheless, causes must be investigated.

We can divide the categories into infectious and non-infectious causes. We commonly think of common infectious causes first (i.e. PNA, UTI etc) - but when this does not give an answer, we must turn to the less common infectious causes and the non-infectious causes.

Infectious Causes

Nosocomial Pneumonia - Consider in a patient with fever, new infiltrates, increased sputum production, leukocytosis and increased oxygen requirements. Have a high suspicion with a recent hospital admission on a patient on the vent. Common pathogens implicated are Pseudomonas and Staph aureus, but instances of Stenotrophomonas and Acinetobacter are non uncommon in our ICUs. Viral causes need to be considered as well. Aspiration pneumonitis, which is usually not infectious, should also be on the differential. Perform trach cultures and then BAL if needed.

Bloodstream Infections - Staph is a common cause, as well as Gram Negatives. Consider Fungal infections (esp. Candida) with long-term indwelling catheters or immunosuppressed patients. You must think of catheter-related blood stream infections in all ICU patients. This is especially true when ANY line is present for >48 hours. If there is purulence at the site of catheter insertion, it usually needs to be removed and the cath tip sent for cultures (>15 CFU is suggestive of catheter related infection). Otherwise, you can draw blood cultures (from the catheter and from a distant peripheral site) - and check time to positivity. There are both quantitative (i.e. >5x colony counts from catheter compared to peripheral) and qualitative guidelines (time to positivity in lab is quicker from catheter than peripheral site) for diagnosis.

Urinary Tract Infections - Suspect in all patients with a Foley. Besides a positive culture, remember that you need both a positive Ua (with WBCs) to help diagnose this. This is because patients with chronic foleys can become colonized, and have positive cultures WITHOUT signs of inflammation on the urinalysis

Wound infections - Make sure to check the skin for infected decubitus ulcers and any other sites of soft tissue infection.

Clostrium Difficile Infection - Suspect with high WBC count, fever, diarrhea in a patient that has received antibiotics or chemotherapy in the weeks prior to the fever. Common antibiotics implicated are cephalosporings, clindamycin and the fluoroquinolones. In some patients fever can be the only initial manifestation of pseudomembranous colitis, so have a high index of suspicion. Send C. diff toxin x 2. If negative and diagnosis is high on the differential, flex sig can be done. Since this is such a severe infection, empiric antibiotics with metronidazole may be warranted while pending culture results.

Sinusitis - Cause of new-onset fever in about 5% of MICU patients. Suspect this in a patient that has a long-term nasogastric or nasotracheal tube. Also seen with nasal packing, facial trauma, and in patients on steroids. Most commonly present in the Maxillary sinuses. Workup with a plan-film of the sinuses and then do CT if the plain films are non-revealing or not definitive. Radiographic evidence alone does not give a definitive answer, so drainage with culture is needed. Most pathogens are Gram Negative Rods (esp pseudomonas, e coli and proteus), but Staph, Candida, are not uncommon.

Abscess - Consider an abscess in a patient that has undergone any surgery or abdominal intervention prior to the surgery. This is not always precedent with these infections, so have a high likelihood for this if no other causes are found. Patients commonly "spike" fevers with these abscesses at about the same time daily. Imaging of the abdomen and pelvis should be considered in the workup

Endocarditis - This can occur without positive blood cultures, especially if the patient is partially treated or has a "culture-negative" cause (i.e. HACEK, psittacosis etc). Especially consider with poor dentition, prosthetic value, or IV Drug use. A TTE may be performed as the initial diagnostic test.

Other infections to consider - Does the patient have meningitis? Do they have osteomyelitis? Do they have peritonitis? Consider these infectious causes as well, even though they might be further down the list on the differential

Non-Infectious Causes

Thrombosis - DVT and PE should be considered in patients. Don't think that being on prophylaxis excludes this. Use the Well's Score and clinical predication rules to determine the possibility. Also, very extensive superficial thrombophlebitis can cause fever - so check all prior and current access sites.

Drug-Induced Fever - Can be from multiple agents. Common drugs are penicillins, cephalosporins, phenytoin, procainamide and quinidine. Usually patients with "drug" fever do not feel "feverish" but can manifest chills and myalgias. Drug rash , leukocytosis and eosinophillia can clue to in to this, but are frequently absent (less than 10-15% of cases!). This is not a common cause, but should be considered when other workup is non-revealing. You should, however consider drug fever in a patient that has relative bradycardia in relation to the temperature!!! Especially consider this with the scenario of an infectious source that is found with temperature initially improving during the admission - then recurring. Treatment is stopping the agent. Usually the fever will resolve in a few days if this is the cause. If the infection is improving, some will actually continue the antibiotics until repeat cultures are negative despite the presence of drug-induced fever. Also consider causes of hyperthermia (in prior blog) - i.e. serotonin syndrome, neuroleptic malignant syndrome and malignant hyperthermia. Consider these when commonly implicated agents are being given, or were recently administered. However, these conditions usually have other findings evident on exam or labs.

Ischemic Disease - Ischemic Bowel Disease or Ischemic Colitis Can produce fever. Not uncommonly, temperature elevations can be seen with myocardial ischemia or CVA. Related to the cardiac system - post MI pericarditis (Dressler's) can also cause low grade fevers.

CVA - Okay, just mentioned above, but should be another category. This is especially common when the posterior fossa or hypothalamus are involved. Subarachnoid hemorrages are also notorious for causing fever in the MICU. Have a high suspicion of this post-trauma, in the elderly, in alcoholics, or in patients with coagulopathy

Acalculous Cholecysitits - Think in our medical patients that are either septic, on a vent, or is getting parental nutrition. Perform U/S as first test. May actually need a CT scan If non-conclusive since HIDAAs in this setting give false positive rates >50%.

Pancreatitis - In the ICU setting, pancreatitis causes by procedures (ERCP), infections and medications should be considered.

Acute Liver Injury - Unless there is an infectious agent present, this is usually due to ischemic causes or drugs. High transaminase levels can clue this into the cause of fever

Endocrine Diseases - Adrenal Insufficiency and Thyrotoxicosis are possible causes. Adrenal Insufficiency in the MICU is more common. Usually the adrenal insufficiency which is severe enough to cause fever is not due to primary causes (i.e. Addisons) or withdrawal of steroids - but from SIRS/Sepsis, adrenal hemorrhage with DIC or other causes, or adrenal infiltration (i.e. TB). Keep Pheochomocytomas in mind as well.

TTP/HUS - Consider this as a cause of fever especially from drug effect (TTP) or infections (HUS). Fever is usually a LATE manifestation of TTP, so be on the lookout for these conditions in the setting of thrombocytopenia or microangiopathic hemolytic anemia. It is not uncommon for MICU patients to have thrombocytopenia, so have a high suspicion and sent a blood smear to look for schistocytes.

Post-Op State/Atelectasis - Fever is not uncommon after surgery, but usually do not produce very high temperatures, and rarely last >72 hours. There is some "controversy" that atelectasis actually causes fever. Some believe that the post-operative state, which causes atelectasis, is the actual cause of fever. Still, this is up for debate...

Alcholol Withdrawal and Delerium Tremens - Consider this could be the cause of fever and a hyperdynamic state in a patient with history of significant EtOH use prior to their MICU admission. Not uncommonly seen with benzo withdrawal, and even fevers reports with opiate or barbiturate withdrawal.

Iatrogenic Causes - There are reports of fevers being reported in the MICU due to faulty equipment (i.e. heated mattresses) - this is not a common cause, but it's certainly a cost-effective element to look for. Sometimes there is a febrile response in patients post-procedure - after endoscopy, bronchoscopy or even post endotracheal suctioning. Make sure there is no reaction due to blood product administration as well.

And as always, with any differential regarding fever don't forget the vast array of rheumatic and malignant causes.

The HIV/Cancer Patient:
Although the above applies to the HIV patient (or any immunocompromised patient), some other considerations include Acute HIV Infection, Higher Suspicion for Meningitis/Encephalitis and Consideration of Typhilitis (necrotizing infection of colon) in cancer patients.

Workup:
This is an approach to workup in the article by Dimopoulos and Falagas:

Treatment

First the Obvious:
1) Find the cause and treat it specifically
2) Until a cause is found, or unless a non-infectious source is obvious - give broad-spectrum antibiotics to those patients that are unstable (which would be the norm in the MICU)

Now the controversy:
Should you just lower the temperature. There are considerable arguments for and against the use of antipyretics. There is no doubt that they should be used in two circumstances: When the temperature is extremely elevated (i.e >103.5 degrees) or when any fever is present in a patient where the state would be detrimental (i.e in the setting of MI or CVA). There is also some evidence in patients with needs for high FiO2, that lowering the fever decreases oxygen requirements. Some will treat routinely to simply lower the temperature - there is evidence in the surgical ICUs that this either increases mortality or makes no difference. Similar evidence is lacking in the MICU patients.

References -
Dimopoulos, G & Falagas, M. Approach to the Febrile Patient in the ICU. Infect Dis Clin N Am 23 (2009) 471–484

Laupland, K. Fever in the critically ill medical patient. Crit Care Med. 2009; 37[Suppl.]:S273–S278

Marino, P. The ICU Book. Lipincott Williams and Wilkins. 2007

Riga, M et al. Rhinosinusitis in the intensive care unit patients: A review of the possible underlying mechanisms and proposals for the investigation of their potential role in functional treatment interventions. Journal of Critical Care (2010) 25, 171.e9–171.e14

Rizoli, S & Marshall, J. Saturday night fever: finding and controlling the source of sepsis in critical illness. Lancet Infectious Diseases 2001; 2: 137–44

April 15th - MHH - NMS and Hyperthermia

2010-04-15T14:24:00.000-07:00

What follows is a quick overview of hyperthermia (most of which comes from my intern lecture on fevers)

What is Hyperthermia?

As opposed to Fever, Hyperthermia is an increase in temperature over the body’s thermoregulatory set-point. This occurs when body metabolic heat production or environmental heat load exceeds normal heat loss capacity or when there is impaired heat loss.

NOTE: These patients usually will have temperature elevations above 102 degrees

Causes of Hyperthermia:
Heat Stroke: Exertional vs. Non-Exertional
Heat Exhaustion
Thyrotoxicosis
Drug Induced (i.e. malignant hypertension, neuroleptic malignant syndrome, serotonin syndrome)
Pheochromocytoma
Central Hyperthermia/Dysregulation (post trauma/CVA)

Some more details related to the drug-induced causes:

Neuroleptic Malignant Syndrome
Background: Seen in about 0.2 percent of patients who receive neuroleptic agents (common ones include haloperidol and chlorpromazine), usually within the first 30 days of therapy. Other drugs implicated include Phenergan and Reglan. Can be seen in patients that rapidly decrease dose of L-Dopa.

Findings: Over a period of 24 to 72 hours there may be symptoms of muscle rigidity, extrapyramidal abnormalities, altered consciousness, and autonomic dysfunction (labile blood pressure, diaphoresis, tachyarrhythmias, and incontinence). Laboratory findings include hemoconcentration with leukocytosis and hypernatremia, acidosis and electrolyte disturbances, rhabdomyolysis, and abnormal renal and hepatic function.

I memember learning this for the USMLE exams to help remember some of the findings with NMS:
F—Fever
E—Encephalopathy
V—Vitals unstable
E—Elevated enzymes (elevated CPK)
R—Rigidity of muscles

Treatment: Stop the offending medication and use cooling blankets. Patients will likely need aggressive volume replacement. Some studies show decreased mortality rate when bromocriptine or amantadine are administered. Dantrolene can be given, but studies show conflicting views regarding efficacy.

Serotonin Syndrome:
Causes: Many drugs/combination implicated: These include MAOIs, TCAS, SSRIs, opiates, cough medicines, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse.

Findings: Fever, Tachycardia, Hypertension with Mydriasis/diaphoresis. LE Myoclonus, Tremor, increased BS/diarrhea, agitation/AMS. This can be differentiated from neuroleptic maligant syndrome by a few findings: The presence of elevated CK, Leukocytosis or muscle rigidity are suggestive of NMS and NOT serotonin syndrome

Treament: Stop the offending agent and give supportive care (including benzos for agitation). More severe cases can be treated with cyproheptadine

Malignant Hyperthermia
Halogenated inhalation agents and depolarizing muscle relaxants (i.e. succinylcholine) are most often responsible for causing this. A positive family history of similar events is common.

Findings: High Fevers and severe muscular rigidity is characteristic: other typical findings include hypotension, tacypnea, tachycardia, arrhythmias, hypoxia, hypercapnia, lactic acidosis, hyperkalemia, rhabdomyolysis, and disseminated intravascular coagulation.

Treatment: Stop the drug, give hydration and oxygen, and start cooling measures. Dantrolene should be given as well. Note that Dantrolene should be given prior to anesthetic procedures when this may occur due to prior events or family history

April 15th - MHH - Aortic Insufficiency

2010-04-15T14:01:00.000-07:00

Today at MHH a patient with endocarditis and severe Aortic Insufficiency was presented. What follows is a quick board-relevant focus on Aortic Insufficiency. One must think of the disease in the context of whether the AI is acute or chronic.

Causes:
The more common causes of Chronic Aortic Insufficiency/Regurgitation are:
Bicuspid Aortic Valve
Aortic Dissection
Infective Endocarditis
Calcific Disease of the Aorta/Myxomatous Degeneration
Marfan Syndrome
Hypertension
Rheumatic Heart Disease
Other Rheumatic Conditions (i.e. Rheumatoid Arthritis, Anklyosing Spondylitis, Reactive Arthritis)

Acute AI is usually causes by one of the following:
Infective Endocarditis
Trauma/Dissection of the Ascending Aorta

Symptoms:
Depend somewhat on whether the patient has acute or chronic Aortic Insufficiency.
Acute AI usually presents with sudden onset of pulmonary edema and dyspnea
Chronic AI usually presents with progressive symptoms of congestive heart failure.
Also - keep in mind the symptoms associated with the cause of AI (i.e. fever with endocarditis)
Physical Exam Findings
Acute:
Patients will present with symptoms of cardiogenic shock - Tachycardia is common. Look for Pulsus Paradoxus. May have difference in BP between both arms due to dissection. The murmur is a very soft diastolic murmur at the LUSB (or it can he heard at the RUSB with aortic dissection). The murmur is actually infrequently heard since the equilibrium of pressures occurs quickly.

Chronic:
Patients with have a widened pulse pressure (Systolic - Diastolic < 100). S1 is soft or sometimes absent. A Decresendo murmur at the LUSB is common (like acute, this murmur may may be at the RUSB with aortic dissection). A concurrent S3 is commonly heard.
Multiple other Physical Exam Findings can be present due to the wide pulse pressure - Muller Sign (uvular pulsation), De Musset Sign (Head bobbing in synchrony with systole), Traube sign (Pistol Shot Femoral Murmur), Durosiez Sign (Femoral Mumur heard with compression), Corrigan Pulse (Rapid Upstoke when quick collapse), Becker's Sign (Retinal Pulsations), Quincke Pulse (capillary pulsations)

Workup:
Should include an EKG (may show Left axis and/or LVH), CXR (cardiomegaly, interstitial pulmonary edema, wide mediastinum?) and TTE. Perform a CT or TEE if suspecting dissection. Most patients should have a serum RPR/VDRL sent.

Treatment:
Acute Aortic Insufficiency will usually need emergent valve replacement. In the meantime, IV nitroprusside or nitroglycerin can be used for preload reduction. Lasix for volume overload. Supportive care with dobutamine should be administered for cardiogenic shock. DO NOT Place an intra-aortic balloon pump!

Medications (i.e. vasodilators such as ACEI, nifedipine or hydralazine) can be given to:
1- Reduce symptoms
2- Patients that have Hypertension
3- Patients with Severe AI that may be asymptomatic, but have LV dilatation

Surgery (AV Replacement) is indicated for:
1- Symptomatic patients that have severe AI regardless of LVEF
2- Asymptomatic patients with severe AI and LVEF <50%
3 -Chronic severe AR when undergoing other cardiac surgery (i.e. CABG)

Prognosis/Followup:
The most important determinant factor is LVEF.
In patients without symptoms and normal LVEF, an echo is required every 2-3 years
In patients with symptoms or decreased LVEF, an echo is needed every 6-12 months

Image References:
www.pages.drexel.edu/~nag38/index.html

April 15th - LBJ - Sterile Pyuria

2010-04-15T12:03:00.000-07:00

Today at LBJ the Renal Service presented patient with HIV that had with multple systemic complaints. They were consults for AKI (baseline Cr 0.9 - now 5.4) and on the Urinalysis the patient had sterile Pyuria. Here is a quick review are the causes of sterile pyuria (Significant WBCs - meaning at least 5-8 per hpf on Urinalysis with few/no bacteria and negative Gm Stain).

Make sure the specimen is obtained appropriately (i.e. clean catch) before making the call of sterile pyuria!!!

Infectious Causes
1) Tuberculosis of the GU Tract (work up with Urinary AFB)
2) Gonnorrhea/Chlyamydia infection (Can send G/C Probe to w/up) or UTI with "other" fastidious organisms (i.e. ureaplasma)
3) Fungal Infections of the Urinary Tract
3) Reports of some Viral Infections of GU tract causing sterile pyuria
4) Recently treated UTI (of any cause) in the last 2 weeks

Inflammatory Causes
1) Prostatitis (without active infection)
2) Appendicitis or Diverticulitis (when adjacent to bladder)

Systemic Diseases
1) Lymphoma of the Bladder
2) Amyloidosis, Leukemia and Myeloma (via causing a chronic interstitial nephritis)
2) Sarcoidosis
3) Malignant hypertension (usually with concurrent hematuria)
4) Kawasaki Disease

Renal Causes
1) Renal Vein Thrombosis (Consider in a patient with nephrotic syndrome + flank pain)
2) Intersititial Nephritis (and it's various causes - Analgesic/Antibiotic/other drug induced, lupus nephritis, Sjogren's, vasculitis, treated pyelonephritis, heavy metals)
3) Renal Papillary Necrosis (can be from NSAID use, Sickle Cell Disease or even obstruction)
4) Nephrocalcinosis (suspect with RTA Type I) and chronic/recurrent nephrolithiasis
5) Cholesterol Emboli Syndrome (Consider with concurrent glomerulonephritis and recent vascular intervention)
6) Polycystic Kidney Disease
7) Interstitial cystitis

------------
References:
Dieter, R. Sterile Pyria: A Differential Diagnosis. COMP THER. 2000;26(3)
Massry et al. Textbook of Nephrology
Fausi et al. Harrison's Principles of Internal Medicine 16th ed

April 9th - MHH - Thyrotoxicosis

2010-04-12T17:57:00.000-07:00

Today at Morning Report a Patient with Thyrotoxicosis was presented

So what does this mean?
Hyperthyroidism is the general term for increased thyroid function
Thyrotoxicosis is sometimes used as a synoynm, but generally refers to increased circulating levels of T3/T4.
Thyroid Storm is a serious complication, usually in untreated patients with infection/surgery/trauma and others

Causes:
Graves Disease
Toxic Multinodular Goiter
Thyroiditis
Thyroid Adenoma
Factitious
Also - Struma Ovarii, which is rare

Some physical signs/symptoms with thyrotoxicosis:
General & Vitals: Tachycardia, Fevers, Heat intolerance, Weight Loss, Anxiety, Insomnia, AMS
HEENT: Graves opthalmopathy ("foreign body sensation," periorbital edema, conjunctival injection, increased lacrimation. Diploplia and Proptosis can be present as well
Neck: Goiter (Look for bruit in patient with Graves)
Cardiovascular: Tachycardia, Systolic Flow Murmur on Exam. Patient may have irregular rhythm due to atrial fibrillation. Remember that thyrotoxicosis can exacerbate/cause CHF or exacerbate CAD
Pulmonary: Dyspnea
GI: Increased stool frequency
GU: Oligomennorhea
Neuro: Tremors and Hyperreflexia (rapid relaxation phase)
Skin: Moist and warm, palmar erythema may be present, pretibial myxedema
Nails: onycholysis

Caveat for the Elderly - There is a term called apathetic hyperthyroidism. Instead of presenting "classically," the elderly can have a complaint of just weakness, weight loss and/or atrial fibrillation

Workup/Diagnosis
Send a Serum TSH. A level <0.1 is consistent, and a Free T4 should then be sent. If the T4 is normal then T3 should be measured, as there are instances of this alone. If the TSH is low in the setting of a Normal T4 or T3 then the patient may have either "subclinical hyperthyroisism" (which would technically be a misnomer if the patient presented with the above signs/symptoms) or Sick Euthyroid Syndrome due to underlying disease. Note in Sick euthyroid syndrome the T4 is common'y either low or normal. You can confirm this state with an elevated reverse T3.

One can order a RAIU to differentiate the causes of hyperthyroidism/toxicosis.
High RAIU States include: Graves Disease, Toxic Multinodular Goiter and Adenoma
Low RAIU States include: Thyroiditis and Factitious Causes

Usually this testing is not always needed as physical findings of Graves disease are obvious in most causes. The presence of eye findings and/or pretibial myxedema is almost always Graves. If the patient has either a diffusely nontender goiter OR a non-palpable thyroid usually have Graves as well

Also - workup the causes of what may have exacerbated the thyroid state - i.e. infection

A Note About Thyroid Storm
This can be caused by infection, surgery, trauma, DKA, Pregnancy
Patients will be very tachycardic (or have atrial arrythmias), fevers, N/V, tremors and AMS and can progress to a comatose state. See below for scoring system:

Treatment for Acutely Ill/Serious Thyrotoxicosis/Storm
PTU 300mg po q6 hours
SSKI 1-2 Drops po q12 hours
Propanolol 40mg po q6hours and titrate if needed

See this link for an article from Endocrinology clinics regarding thyroid storm, with the scoring system:
http://www.scribd.com/doc/6837836/Thyrotoxicosis-and-Thyroid-Storm

April 6th - LBJ - Multiple Myeloma/Amyloid

2010-04-07T09:15:00.000-07:00

Today at Morning Report a Case of Multiple Myeloma was Presented. Here is a brief overview of the disease and what you'll need to know for boards regarding plasma cell disorders and amyloidosis

Multiple Myeloma is the most common malignant plasma cell dyscrasia. There are many other malignant and secondary plasma cell disorders, most of which are beyond what you'll need for boards. Also keep in mind there are various subsets of non-malignant plasma cell disorders (i.e. MGUS) which you should be aware of

Multiple Myeloma - Presenting Symptoms/Physical Exam
General - Fatigue and Weight Loss are Common
Anemia - Pallor is the most common finding on examination
Bone Pain, Osteopenia and Pathologic Fractures - From Osteoclast activity and Lytic Lesions
Renal Failure - Symptoms of azotemia from light chain deposition or calcium impairment of renal perfusion
Nephrotic Syndrome - Can present with edema, increased risk of thrombosis
Hypercalcemia - Can present as various symptoms (i.e. confusion, renal stones, constipation etc)
Recurrent Infections - Due to Immunglobulin Disease
Bleeding Tendancy - Platelet and Coagulation Dysfunction
Neurologic Complications - Radiculopathy, Cord Compression, Polyneuropathy
Leukostasis - Uncommon, but with a very high plasma cell burden - patients can get Blurred Vision/Headache/Heart Failure/Dyspnea.

Always think of Myeloma in a patient (especially elderly) with anemia, renal failure and hypercalcemia

Lab Findings/Workup/Diagnosis:
In General, to diagnose Multiple Myeloma we use the Working Group Criteria or the WHO Criteria. Although there are other lab findings that are not specific parts of the diagnostic criteria. In general, the WHO criteria are a bit more pathology based, and the Working Group is more clinically based. I'll put both of them here so you are aware:

WHO:
The diagnosis of multiple myeloma requires a minimum of one major Criterion + one minor criterion OR
three minor criteria with bone marrow plasma cells >10% or a monoclonal protein

Major criteria
I Plasmacytoma on tissue biopsy
II Bone marrow plasmacytosis with > 30% plasma cells
III Monoclonal globulin spike on serum electrophoresis (> 3 g/dL for IgG, > 2 g/dL for IgA) or on concentrated urine electrophoresis (> 1g/24h of k or l light chains)

Minor criteria
Bone marrow plasmacytosis 10 to 30% plasma cells
Monoclonal globulin spike less than the level defined above
Lytic bone lesions
Residual normal IgM <0.05 g/gL, IgA < 0.1g/dL, IgG < 0.6g/dL

Working Group:
1 - Monoclonal Plasma Cells in Bone Marrow >10% OR a plasmocytoma on biopsy
2 - Monoclonal Protein in serum or urine (send SPEP and UPEP with IF and Serum Light Chain Analysis)
3 - Any one of the following organ related diseases:
Calcium Elevated, Renal Insufficiency, Anemia, Lytic Bone Lesions or Osteopenia

Other Lab Findings in patients with myeloma:
BUN decreased
Negative anion Gap acidosis
Proteinuria of various severity on Ua
Globulin Gap
Alk Phos is NORMAL (remember this increases with blastic disease, not lytic disease)
Send LDH and B2 Microglobulin for staging and prognosis

Treatment:
The mainstay of treatment is supportive care:
Transfusions for severe anemia and most patients should get EPO for anemia
Dialysis for Renal Failure
Bisphosphonates for lytic lesions
Saline and bisphosphonates for hypercalcemia
Prophylactic immunizations
Monthly Immune Globulin Infusion for recurrent infections
Radiation Therapy for Plasmacytomas or refractory bone pain

Remission is rare in patients, and is usually best achieved with autologous bone marrow transplantation. However, this is usually offered to patients that are <70 years old with good performance status - and unfortunately most patients with myeloma do not fit into this category

Positive Response to treatment is seen in about half of patients that recieve various combinations of treatment - including alkylating agents, steroids, anthracyclines and thalidomide. Chemotherapy regimens including doxorubicin and vincristine are used with treatment failure. Lenalidomide, an analog of thalidomide, has less side effects (i.e. less fatigue) but also carries the risk of thromboembolic disease. Bortezomib is a proteasome inhibitor that has been used as well.

Non-Malignant Plasma Cell Disorders. Most are here to be completen, but you should really know MGUS for boards:
1) Monoclonal Gammopathy of Undetermined Signficiance - Less than 10% Plasma Cells with no symptoms or systemic complications. This is present in about 2% of patients >50 years olf. Annually, about 2% of patients transform into Myeloma - and about 20% will get myeloma during their lifetime. So, these patients need regular SPEP and UPEPs and physical exams/visits with clinicians to look out for progression to myeloma. BM Bx will be needed in patients with MGUS that have concerning signs/symptoms that are a change from their regular status. MGUS is seen in the general population, but is seen with increased incidence in those with autoimmune diseases, cirrhosis, and HIV

2) Smolering Myeloma - Plasma Cells greater than 10% but less than 30% without signs/symptoms

3) Indolent Myeloma - Plasma Cells greater than 10% but less than 30% with only mild anemia or <3 lytic lesions

Waldenstrom's Macroglobulinemia
This disease is causes by increased secretion of IgM paraprotein by plasma cells (as opposed to IgA or IgG in Myeloma.) Can present very similar to MM, but these patients are at a higher risk of getting a hyperviscosity syndrome (CHF, AMS, MI, CVA, Retinal Complaints) and organomegaly is common. Treat hyperviscosity with plasmapheresis + Chemotherapy (agents used include rituximab, chlorambucil or fludarabine)

Amyloidosis:

Think of AL Amyloidosis in a patient with any plasma cell dyscrasia that has a change in symptoms (especially CHF). There are multiple other forms of amyloid (i.e. AA and inflammatory conditions such as Familial Mediterranean Fever)

There are multiple findings/clues for amyloid:

General: Constitutional Symptoms
Skin: Purpura around face, neck, eyelids, “Shoulder Pad Sign,” Nodules
CV: Congestive Heart Failure Symptoms, Conduction Blocks, Arrythmias
GI: Dysmotility, Obtruction, Organomegaly
Heme: Anemia, DIC, Bleeding
Nervous System: Paresthesias, syncope, changes in bowel movement, carpal tunnel
Other: Change in Voice/Macroglossia

Remember that CHF is the cause of Death in over half of patients with myeloma. They will have a restrictive pattern of filling, and classic septal hypertrophy changes/"snowstorm" appearance of the septum:

Diagnosis of Amyloid:
Biopsy of an affected site will give the best yield. So if there is renal failure you may consider renal biopsy. This will have the highest yield, but of course risks vs benefits must be weighed. Other less invasive ways to diagnose include: Abdominal Fat Pad or Rectal Biopsy for Congo red stain (looking for apple-green bifringence). These have a reported diagnostic yield of between 70-85%

Treatment:
Best survival with high-dose melphalan and stem cell transplant, but this is not offered to most patients

References:
Images Courtesy of:
University of Virginina Dept of Heme/Onc &
http://www.stanfordhospital.org/ - information page on AL Amyloidosis

April 6th - MHH - HIV and Shortness of Breath

2010-04-07T07:51:00.000-07:00

Today at Morning Report a Case of Dyspnea in a Patient with HIV was discussed. The differential for patients with HIV/AIDS presenting with dyspnea is varied, and one must add additional conditions not seen in immunocompetent patients. Here is a general thought process to causes in these patients

Infectious Causes
Bacterial Pneumonia (i.e. "Community Acquired") is your number one thought in this category, as strept pneumoniae is the most common pathogen in HIV patients. They are also at an increased risk of getting empyemas. If you see an effusion or consolidation, think this bug first. Blood Cultures, Sputum Cultures and Urine Antigen can be sent, but you must think of this diagnosis clinically.

PCP/PJP - We see this very commonly, especially in patients with CD4 Counts Less than 200. The "Classic" presentation is dyspnea on exertion, fever, scant productive cough and hypoxia that is progressive and worsened with exertion. We all Send LDH Levels - the Sensitivity in studies ranges from about 86-97%, but the specificity hovers around 50%. CXR can show the "batwing" appearace - but PCP can appear as any bilaterial or unilateral infiltrate. Early in the disease, the CXR may be negative. Sputum Cultures can be sent for diagnosis, but the sensitivity is about 40%. In patients with suspected PCP and negative sputum cultures, bronch should be performed. Treat with Bactrim and add Steroids is the Pa02<70 or the Aa Gradient >35.

Viral Causes - Especially CMV

Fungal Causes - Histoplasmosis and Crypto are high on the list, especially in Houston. Keep Blastomycosis in mind with Skin Lesions, and Coccidio with contact in the endemic SW region.

Tuberculosis - Even if you are thinking PCP, sputum cultures for APB can be considered. A PPD can be placed, but doesn't tell you as much...

Atypical Mycobaterium - i.e. MAC. Have a high suspicion especially with CD4 Counts below 50, although not uncommon in counts <100. Send Sputum Cultures. If they stain Acid Fast Bacilli, you would usually treat for MTB untill the PCR/culture reveals an atypical organism. Although, most would add a macrolide to the treatment regimen while awaiting final cutures, when they have a high index of suspicion of atypical mycobacterium.

Malignancy

Lymphoma - Both NHL and Hodgkin's should be considered. In general, NHL (especially B Cell Types) are highest in these patients. Common forms include Burkitts, DLBC, and Large Immunoblastic Lymphoma. Keep in mind, that the incidence of Hodgkin's Lymphoma is increasing in the HAART era, and is rising in patients on treatment for HIV. The tumor burden in the lungs alone/mediastinal involvement can cause dypnea. Always consider that this may be happening with your patient as the CXR with lymphoma can easily mimic infectious causes.

HHV-8 Associated Malignancies - Kaposi's Sarcoma involving the Lungs, Castleman's Disease (A lymphoproliferative disorder) and Primary Effusion Lymphoma

Consider other Malignancies - Think both Primary Lung Cancer and Metastatic Disease. HIV increases the risk of Primary Lung Cancer regardless of smoking, and there is evidence of increased risk of metastatic spread of other primary cancers.

Lung Disease

Interstitial Lung Disease - Nonspecific interstitial pneumonitis and lymphocytic interstitial pneumonitis are very prevalant in HIV patients.
There is also reported evidence of increased incidence of pulmonary alveolar proteinosis and desquamative interstitial pneumonitis.

Pneumothorax - A result of PCP/PJP infection, or various other secondary causes

Pulmonary Hypertension - Remember that HIV is a cause of seconary Pulmonary HTN

Pulmomary Embolism

Cardiac Disease
Congestive Heart Failure - Especially Dilated Cardiomyopathy with HIV

Pericardial Effusion/Tamponade - HIV, Fungal, TB, Malignant Causes

Ischemic Heart Disease - There is evidence of increased risk of CAD with HIV and some interesting papers that Protease Inhibitors contribute to this

Other Causes to Consider:
Rheumatic Diseases - i.e. Vasculitis
Drug Reaction
Anemia (Acute - bleed from carcinoma or other various causes of colitis in HIV Patients. Chronic - consider BM suppression from HIV itself or other malignant/infectious causes - although this is less likely to causes acute dyspnea)

Image courtesy of City University of New York
www.brooklyn.cuny.edu/bc/ahp/SDPS/AtomOxygen.html

February 5th - MHH - Polyuria and Diabetes Insipidus

2010-02-08T08:07:00.000-08:00

Today at Morning Report, Endocrine consults presented a patient in her third trimester with polyuria and polydipsia. Here is a general approach to a patient with polyuria, and info on DI

In general, polyuria is defined as at least 3L of urine a day. The frequency of urination does not matter as much as the total amount. Patients with polyuria will commonly also have polydipsia (to compensate, as long as their thirst center is intact) and will have nocturia.

The basic causes to know for rotations and the boards are:
Diabetes Mellitus
Diabetes Insipidus (Central and Nephrogenic) - and their multiple causes
Primary/Psychogenic Polydipsia
Diuretic Use (esp in those using it for weight loss)
Hypercalcemia
Medications (either directly or by causing a nephrogenic DI)
Post-ATN or Post-Obstrutive Uropathy

Your exam in these patients may show signs of dehydration, although this is not as common when the patient has an intact thirst mechanism. A Good neurologic examination is essential with the variety of causes of central DI. Further examination is directed mostly to other causes of Central/Nephrogenic DI or primary polydipsia (i.e. skin findings with sarcoid, amyloid infiltration, lymph nodes with systemic lymphoma, etc)

For the boards, a key topic is being able to identify and contrast Central Diabetes Insipidus, Nephrogenic Diabetes Insipidus and Primary Polydipsia

Central Diabetes Insipidus occurs from inadequate secretion of vasopressin.
Causes: There are familial/inherited forms, but this is not as common as other causes - tumors of the CNS (including lymphoma and mets), trauma, granulomatous disease (TB/Sarcoid), infections (meningitis) and Sheenhan Syndrome.

Nephrogenic Diabetes Insipidus occurs from renal insensitivity to vasopressin.
Causes: This is commonly an inherited disorder, but can be secondary to medications (esp Lithium, Ampho B), systemic conditions (amyloid, Sjogrens, sickle cell disease, pregnancy), or electrolytes (HyperCA and HypoK)

Primary Polydipsia is simply increased water intake, usually psychogenic in nature (but can also be seen with lesions that affect the thirst center of the brain - sarcoid is a commonly tested one.

Labs: Basic workup should include ruling out causes listed above, if not already obvious. The best test to do initially is a BMP and Urine Osmolarity. Patients will not be hypernatremic if they have an intact thirst mechanism, so don't rule out any of the above three if the patient has access to water, and takes in an amount to offset their urine output. Undiagnosed DM and secondary osmotic diuresis can be ruled out with the glucose on the chemistry. The electrolytes are also very important - both Hypercalcemia and Hypokalemia can not only cause polyuria, but in most cases, will make the symptoms worse as they interfere with the kidneys ability to concentrate urine. Therefore, check these labs and correct as needed.

Urine Osmolarity will be low in patients with Both forms of DI - generally <200. This is usually also the case with Primary Polydipsia. This is the general first step, although it makes sense because of very dilute urine.

The other test that is done is the much heard about water deprivation test. Patients are to be started on this protoco , and are instructed to not drink for about 2 hours before coming to the clinic or hospital for testing. During the time frame, the patient is not given access to fluids -> dehydration -> maximum stimulus for Vasopressin Secretion. Basic labs are drawn, and both Urine Volume/osm are measured every 2 hours. During this time frame, patients with Primary Polydipsia will be able to concentrate their urine. Therefore, in patients with Primary Polydipsia, the Urine osm will rise during the test. In patients with both Central and Nephrogenic DI, the urine osm does not change much, yet the serum sodium may increase.

So, now with no change in urine osm, the patient has either Central or Nephrogenic DI. How to tell apart - the patient is given desmopressin and we see what happens to the Urine Osm. Those patients with Central DI will have at least a 50% increase in the Urine Osm after this medication, whereas patients with nephrogenic DI will have none or a slight increase (<10%) in their urine Osm. In those with primary polydipsis, the urine osm will increase at least 50% as well.

Of NOTE: On Boards, some other lab info/approaches may be given to differentiate the conditions. With a low urine osm, and without the use of the water deprivation test, desmopression may be administered to see what happens to the urine osm. If it changes >50%, then it is central DI. Also, on various board review materials, they mention measuring ADH during the deprivation test. This is usually not done much clinically. You should be aware that with the water deprivation test - a rising plasma osm with no change in ADH is Central, and a rising ADH with no change in urine osm is Nephrogenic. This makes sense, and may be presented on boards - but is not usually the way to diagnose this clinically.

Treatment:
Central DI: Usually get intranasal Desmopressin lifelong
Nephrogenic DI: Treat the underlying disorder/change medications. Treatment is also thiazide Diuretic +/- K-sparing diuretic (The cause voume contraction sensed by the kidneys, and the resulting autoregulatory decrease in GFR will help decrease Urine Output)

Reference:
Image Courtesy of www.operationalmedicine.org

February 2nd - MHH - Mesenteric Ischemia and Ischemic Bowel Disorders

2010-02-04T16:48:00.000-08:00

Today at Hermann, a case was presented regarding a patient with post-prandial abdominal pain (and also history of coronary artery disease and PVD). The diagnosis was Mesenteric Ischemia (aka "Intestinal Angina")

Housestaff frequently interchange the different ischemic diseases of the bowel, and I've hear the term "ischemic colitis" to describe the clinical scenario above. Here is a review of the different ischemic disorders involving the bowel.

There are essentially 4 ischemic disease that affects the mesentery - acute and chronic mesenteric ischemia, mesenteric thrombosis and ischemic colitis. Keep in mind, that each of these has a variety of causes (see below).

Mesenteric Ischemia
In almost all of the causes, the presentation is similar - post prandial abdominal pain, weight loss and "fear of eating." Most of these symptoms occur indolently, yet depending on the cause, this symptoms can present more acutely. The symptoms simply occur from a supply/demand mismatch, and the SMA is the usual site of involvement.  Overall, these patients DO NOT present with blood in the stool/diarrhea.... that is unless there is another overlapping cause that leads to gut infarction. This overlapping cause is usually caused by severe hypovolemia, cardiogenic shock or sepsis.

On exam, the classic presentation is that the patient's complaint of pain is out of proportion to the exam. In fact, the way that patients describe pain - one may suspect that they would have peritoneal signs, but they are essentially non-tender during the exam. (Remember, however, that this would not be the case if there was gut infarction that resulted from an overlapping cause). In all patients, Auscultation of the abdomen may reveal a bruit.

   Acute Mesenteric Ischemia - These patients usually present acutely, and are the highest risk of developing infarction of the bowel. There are a variety of causes, but in all - patients have poor perfusion of the colon - usually at the area of the SMA

Embolic Disease: Common causes of this include atrial fibrillation, or a mural clot post myocardial infarction.This is sometimes seen after vascular surgery as well. Emesis is usually present.

Mesenteric Arterial Thrombosis: Usually causes by rupture of an atherosclerotic plaque. Patients present usually when precipitated by low-flow states. These cases commonly develop gut infarction/necrosis rapidly.

Non-occlusive disease: Hypotension from a variety of causes (MI, Sepsis, etc), vasopressors, cocaine and Digoxin

Workup of Acute Mesenteric Ischemia:  CBC (may have elevated white count, and usually hemoconcentration occurs), Amylase usually elevaed. Can have a lactic acidosis. KUB (to rule out other causes) may have findings later in the disease course (especially c/w SBO). CT may be helpful, but mostly to rule out other causes of abdominal pain. Diagnosis is usually done via angiography, which is currently preferred over MRA.

Treatment of Acute Mesenteric Ischemia: This is an emergency, as it can rapidly progress to bowel infarction and gangrene   During angiography, thrombolytics can use used with ischemic disease. Some may need angioplasty or stents afterwards if there is atherosclerotic disease. Less emergent cases can be treated with Heparin or LMWH. If there are any signs of infarction (peritonitis, acidosis, lactic acid up) - then emergent surgery is needed

Chronic Mesenteric Ischemia - Over 90% of patients with this have atherosclerotic disease as the cause. They usually have more chronic symptoms, and although they rarely get gut infarction, they have a high risk of emboli/thrombosis which can lead to infarction. Think of this as the cause of abdominal pain in a patient with risk factors for coronary artery disease (esp Smoking, DM, HTN, Dyslipidemia) and/or have a history of CAD/MI/CVA/PVD.

Workup of Chronic Mesenteric Ischemia: Mostly done to rule out other causes (i.e. liver disease, pancreatitis, biliary disease, nephrolithiasis, etc). Angiography is the gold standard for diagnosis.

Treament of Chronic Mesenteric Ischemia: Stenting of the SMA. If this is not possible, endarterectomy or bypass can be performed

Mesenteric Venous Thrombosis - Usually presents acutely, but can be chronic. Causes by other things you would think of causing venous thrombosis - hypercoaguable states (esp Factor V Leidin, Protein C/S, PNH), pancreatitis, cirrhosis and sickle cell disease.

Patients present very similarly to those with mesenteric ischemia - post-prandial abdominal pain, "fear of food" and weight loss. The exam is the same as well - essentially non-tender although the patient complains of a lot of pain. Bruits are not usually heard.

Workup: Rule out other causes of abdominal pain. CT scan is the test of choice. Once imaging shows findings c/w a thrombosis - then workup the cause.

Treatment: Consists of heparin/LMWH then long-term coumading. Thrombolysis for emergent cases. Surgery is signs of infarction/peritonitis develop.

Ischemic Colitis (aka Colonic Ischemia - confusing huh?)
These Patients have a non-occlusive cause of their disease. Unlike the above causes, which invariably affect the SMA, this disease usually affects the IMA. Especially involved is the so called "watershed area" of the splenic flexure.  Any area distal from the splenic flexure, however, can be involved.

There are multiple causes of this - mostly post-operative, low-flow states, hypercoaguable states, vasospastic drugs (cocaine), vasculitis and history of radiation exposure. Embolism post MI or from Afib is RARELY the cause.

These patients present very different from mesenteric ischemia. The presentation is almost always acute, with pain on the left side of the abdomen. These are the patients that present with a sequence including strong urge to defecate then diarrhea without blood then diarrhea with blood. Low grade fever may be present, as well as nausea and emesis. They are usually very tender on physical exam.

Workup: KUB to r/o other causes, as well as labs to investigate pancreatitis, infectious causes, and other mimics. Colonoscopy is diagnostic (will show mucosal hemorrhage).

Treatment: Supportive care - fluids, NPO and antibiotics if severe. Patients can progress to gangrene of the gut, and will need immediate surgical resection.

January 26th - LBJ - Nephrotic Syndrome

2010-01-27T21:00:00.001-08:00

Today at LBJ, a case of nephrotic syndrome was presented. Although the exact diagnosis for this patient is not known (biopsy results pending), for boards you should know the basic causes of nephrotic syndrome - as well as further work-up and treatment

Lab findings/Diagnosis: The classic necessary finding in nephrotic syndrome is proteinuria (usually at least 3+ on urine dipstick, but a 24-hr urine protein of >3grams or a spot Urine Protein/Cr ratio >3 is more specific). Patients will also have hypoalbuminemia, dyslipidemia (LDL and TG), HTN and hypogammaglobulinemia. There is usually not as much inflammation as in patients with nephrotic syndromes, with some exceptions - but in most patients there will not be hematuria or dysmorphic RBCs/RBC casts. While pending biopsy, serologic workup can be performed (you'll see why below) including HIV, ANA, anti-DS DNA, Complement Levels, RPR, Hepatitis Panel and Serum Protein/Urine Protein Electrophoresis with IF. Remember to get a good review for all OTC medications taken as well. Workup in most adult patients will require a biopsy for ultimate diagnosis unless the cause is obvious (i.e. diabetic).

Clinical: Patients can present with HTN, Foamy Urine, Edema (starts in dependant areas - such as periorbital, scrotum and legs - but patients can eventually get anasarca/pleural effusion/ascites), infections (due to low gamma globulins), and thrombosis (Lower extremity, pulmonary embolism and renal ven thrombosis due to loss of AT-3). How does renal vein thrombosis present? -Acute abdominal pain + sterile pyuria should clue you in to this entity

Like the causes of glomerulonephritis, one can think of causes of nephrotic syndrome in two categories: Those that are systemic diseases, and those that cause more specific changes on biopsy

The systemic diseases that cause nephrotic syndrome:
1) Diabetes Mellitus - the most common! Remember the A1c can be normal in those patients that have developed some element of renal insufficiency. These patients usually do not need a renal biopsy to diagnose, and this is usually a clinical diagnosis. Patients should be placed on an ARB/ACEI and a low protein diet. Patients that do not have good glycemic control, uncontrolled HTN, and keep spilling protein will get progressive decrease in GFR. This is usually not too rapid, and occurs over a number of years.

2) SLE - Can also present with a more "nephritic" component. Remember, SLE can affect the kidney in a variety of ways...

3) Multiple Myeloma - Patients will present clinically with: high globulin gap, bone pain, anemia, renal failure, hypocalcemia. They might not have frank nephrotic syndrome on presentation, and might just has +1 protein in their urine. Still, a work-up for this must be done for patients with nephrotic syndrome (SPEP/UPEP with IF)

4) Amyloidosis - usually caused by light chain deposition, or from AL forms. On the boards, these patients will have other clues/findings (such as restrictive heart failure, neuropathy, etc)

The Renal "Causes" of nephrotic syndrome
1) Minimal Change Disease - In adults, the causes can be Idiopathic or caused by NSAIDS or Hodgkin's Lymphoma. Biopsy shows "effacement of foot processes" Treat with steroids +/- cytotoxic agents (such as cyclophosphamide)

2) Membranous Nephropathy - There are MULTIPLE causes for this on biopsy.
    Drugs: NSAIDS, Gold
    Autoimmune Disease: SLE
    Cancer: Solid tumors, especially HCC, RCC, Colon and Lung
    Infections (HCV, HBV, HIV, Malaria)
       These patients usually have the underlying condition treated/removed first, and if
     severe disease, get  steroids +/- cytotoxic agents

3) Focal Segmental Glomerulosclerosis - has MULTIPLE causes as well
     Idopathic (esp with h/o HTN), Sickle Cell Disease, Heroin use, Obesity.
     Steroids are usually given to treat, but most end up needing Dialysis

Overall, patients with nephrotic syndrome should be placed on ACEI/ARB and diuretics as needed. Good BP control is essential. Many patients need to be on medications for dyslipidemia. A word about anticoagulation - these patients are "hypercoaguable", so do they all need treatment? Usually when inpatient - only DVT prophylaxis is given. Life-long treatment is usually given to patients with one thrombotic event. Prophylactic treatment to prevent an occurance of a thrombosis is not usually done, except in some cases of membranous nephropathy.

January 25th - MHH - Scleroderma

2010-01-27T21:00:00.000-08:00

At MHH, a case of CREST Syndrome was presented - here is a brief overview of scleroderma - subtypes, lab findings, and management.

For internal medicine boards, you should be familiar with the systemic forms of scleroderma (as opposed to those which only dermatologists treat)

The first is Limited Systemic Sclerosis (used to be called "CREST" syndrome - which is a good way to remember the salient features)

These patients will have findings that go along with the CREST letters - Calcinosis, Raynaud's phenomenon, Esophageal Dysmotility, Sclerodactyly and Telangiectasias. These patients usually only have skin changes in their extremities distal to the wrist, and mostly in the upper extremities.

Other findings and complications in these patients include:
-Hyper/hypo pigmentation of skin
-Tight skin around face/paucity of wrinkles/"mouse facies"
-Digital ulcerations and ischemia
-Arthritis
-Lung disease (pulmonary HTN)
-"Watermelon Stomach"/Gastric vascular antral ectasia and GI Bleeding. Bacterial overgrowth and malabsorbtion can occur as well

Lab findings: ANA (>90%)and anti-centromere staining pattern of ANA (50%)

Treatment:
Raynaud's: Warming of fingers, calcium channel blockers
Digital ulcers: warming of extremities, aspirin, topical nitrates and prostacyclins
Esophageal Dysmotility: Almost all patients are on PPIs. May need Feeding tube placed
Pulmonary HTN: Supplemental Oxygen, Calcium channel blockers, bosenten, prostacyclins

Other category is Diffuse Systemic Sclerosis:

Clinically these patients have skin involvement more proximal to the wrist, and also have involvement of the torso/face. Although these patients will have some overlap features of the CREST syndrome (especially telangiectasias, "mouse facies" and Raynaud's), in general organ invovlement is more prevalent:

MS: Abnormal nailfold capillaries, arthritis may be present, tendon friction rubs,
myositis and myalgias
Lungs: Patients can develop interstitial lung disease and pneumonitis
Renal: Scleroderma Renal Crisis (HTN, Renal Failure and hemolytic anemia)
GI: Malabsorbtion, bacterial overgrowth and primary biliary cirrhosis
CV: Fibrosis, Myocarditis, CHF, Pericardial Effusions

Labs: ANA (>90%) and scl-70 (30%)

Treatment: Patients get treated for systemic sclerosis with steroids when organs are affected (i.e. Heart and Lung). Cyclophosphamide is used for intersititial lung disease, and other cytotoxic agents are added with heart involvement. Scleroderma renal crisis is treated with ACEIs. Arthritis is usually treated with NSAIDS and Acetaminophen. Remember, steroids are not given to all patients - only when there is some element of systemic involvement, or myositis.

January 22nd - MHH - Lung Cancer

2010-01-23T14:25:00.000-08:00

Today at morning report, a 47 year old AAF with significant tobacco use presented with 2 months of worsening dyspnea on exertion. Although the final pathology was not back, it is likely small-cell lung cancer.

On the boards, the info you'll need to know for Lung Cancer is broad, so here is a quick review. I would be familiar with staging - although the boards will not likely ask you to stage, they may ask a questions regarding treatment modality. To know this, you need to know the stage.

Risk Factors: Smoking (increases risk about 15x normal. Even 2nd hand smoke exposure increases risk about 2x), asbestos exposure, other heavy metal exposure

Clinical Presentation: Over 90% of patients with a diagnosis of lung cancer have some sort of symptoms - either from local involvement, paraneoplastic syndromes or metastatic disease. Local symptoms depend on the location of the lesion. So the more "central" cancers (i.e. small cell and squamous cell) present with bronchial obstruction, pneumonia, cough, hemoptysis and dyspnea. The more "peripheral" cancers can present with pleurisy, chest wall pain and pleural effusion. Obviously either can cause dyspnea as well as cough/hemoptysis, and there is some overlap. Think of lung cancer in a patient with a history of COPD that presents with an "exacerbation" that is different than their usual exacerbation (i.e. more severe, or lasting longer). Also consider with new onset COPD symptoms in an older patient. Other signs/symptoms include change in voice, Horner's Syndrome, arm paresthesias, SVC syndrome, clubbing, temporal wasting and lymph node enlargement. Metastatic disease can present with bony pain, headache/AMS, or hepatomegaly. We'll go over paraneoplastic syndromes in a bit as well.

Diagnosis: CXR for initial suspicion, followed by CT Scan. You ideally want to biopsy any lymph nodes first, but can also biopsy the mass. Bronchoscopy can be used for central lesions that are >4cm. Open biopsy or IR-guided biopsy if the lesion is peripheral or small.

Classification/Pathology and Subtypes:
Small-Cell Carcinoma
Non-Small Cell Subtypes (includes squamous cell, large cell and adenocarcinoma)
Others: carcinoid and rare pathology (carcinoid is reviewed in one of my earlier posts)

Small Cell Carcinoma
Usually metastasize early, as compared to the non-small cell types. Located more "central" Paraneoplastic syndromes include SIADH, Eaton-Lambert and ectopic ACTH production.

Staging for Small Cell:
Limited: Can fit within one radiation therapy Port (Confined to one Lymph Node, the Mediastinum and A Supraclavicular LN)

Extended: If it does not fit into one port

Treatment for Small Cell:
Limited: Cisplatin + Etoposide with Radiation

Extensive: Cisplatin + Etoposide or Carboplatin + Etoposide
If Brain Metastases are Present - Radiation and Steroids (Some give prophylactic cranial irradiation for both stages, although it is more controversial for Limited-Stage Disease)

Non-Small Cell Subtypes:
Squamous Cell - Most likely to cavitate. Central Lesion. Hypercalcemia
Large Cell - Peripheral. Mets to CNS
Adenocarcinoma - Peripheral. Seen 50% of the time in non-smokers. Bronchoalveolar carcinoma is a subtype of adenocarcinoma that looks like pulmonary edema/diffuse interstitial infiltrates

Staging for Non-Small Cell:
Stage I: <3cm and no LAD or Mets
Stage II: Hilar LAD or Chest Wall
Stage III: Mediastinal LAD
Stage IV: Mets

Further Workup for Non-Small Cell:
PET Scan
Mediastinoscopy for LN >1cm
CT and MRI of Head usually needed
Bone Scan if symptoms of bone pain or increased Alk Phos
Treatment for Non-Small Cell:
Stage I and II: Sx and Chemo (Debate if radiation is added to this – it may increase mortality).

Stage III: Chemo and Radiotherapy
Stage IV: Chemo for patients with good Performance status

Chemotherapy for Non-Small Cell usually consists of:
Paclitaxel+Carboplatin or

Cisplatin+Etoposide
Adenocarcinoma: Oral Gefitinib used at times

Here is a chart I made comparing "high-yield" basics for the 4 types:

Paraneoplastic syndromes - the boards like these, so know them cold!
SIADH - Hyponatremia (what are the labs with SIADH? UNa>50 and Uosm>200) - Small Cell
Hypercalcemia and it's multiple symptoms - usually squamous cell
Acromegaly - GH secretion usually from small cell subtype
Cushing's Syndrome - ACTH secretion from small cell subtype
Hypertrophic Pulmonary Osteoarthropathy - New periosteal bone formation - usually adenocarcinoma
Lambert Eaton Syndrome - Proximal Muscle Weakness, autonomic dysfunction (impotence and dry mouth) with areflexia and sparing cranial nerves The amplitude of action potentials on EMG, and symptoms, improve with repetitive stimulation. This usually occurs with Small Cell Subtypes. (Remember that Myasthenia has cranial nerve involvement, normal reflexes, and worsening with repeated motion)

January 22nd - MHH - All about the Pituitary

2010-01-23T08:38:00.000-08:00

Today at Morning Report a case of a piuitary mass in a patient with history of treated prolactinoma was presented. Here is an overview of pituitary masses, pituitary disorders, and more on prolactinomas

Pituitary Mass:

Clinical Symptoms: Pituitary masses cause one of two major categories of symptoms - those of mass effect and those of either hypersecretion or hyposecretion of hormones. Mass Effect from tumor growth can cause headache, seizures, diploplia, blurry vision and/or visual deficits.

When you see a pituitary mass, you should order the following:
TSH and FT4
Prolactin
Alpha Subunit (marker produced by GH) and IGF-1
FSH/LH
Cortisol
Estradiol in Females
Testosterone in Men

Specific Symptoms: Will depend on hormone effects, some of which include:
Patients can get S/Sx of hyper/hypothyroidism
Patients may get cushing's disease or adrenal insufficiency (the former is more common)
Acromegaly may result as well
Prolactinoma symptoms (more below)

Treatment: Depends on treating the causes of hormone excess or deficiency. Surgery is usually used in these cases as well.

Prolactinoma:

Classified as microadenomas (<1cm) or macroadenomas (>1cm). Usually macroadenomas cause visual field defects, but microadenomas are more common overall

Symptoms: In Men - Loss of libido, impotence, loss of peripheral body hairDiagnosis: Imaging (MRI) and Prolactin Levels. You should work these patients up for "pituitary masses" as stated above - importantly obtaining a TSH (to rule out secondary elevated PRL caused by an elevated TRH level OR concurrent hypothyroidism) and cortisol levels, in addition to other hormones.

                      In Women - Amenorrhea, galactorrhea and hirsutism
                      If the tumor is large enough, compression of nearby cells can lead to deficiency
                                of other hormones - commonly TSH, GH and ACTH.
                      And of course, mass effect symptoms depending on size of tumor


So, in morning report there was some discussion was raised about levels of Prolactin. What is normal? How high of a levels leads you to suspect prolactinoma? What else raises levels of PRL?

Normal: <25ng in females, <20ng in Males and Children
40-85 ng: Craniophayngomas, Hypothyroidism and Drugs (esp anti-emetics, antipsychotics and TCAs
~50ng: 25% chance of pituitary tumor and ~100ng: 50% chance of pituitary tumor
>150ng: Usually a prolactinoma, and if the level is >200 it is about 100% chance of being a prolactinoma

Other causes of increased prolactin include:
Any pituitary lesion
Hypothalamic Lesions (histiocytosis X, sarcoid, TB, glioma)
Endocrine: Hypothyroidism, Addison's Disease, Glucortocoid Excess, COS
Ectopic production: Bronchogenic carcinoma, RCC
Neurogenic: Post-Seizure, Spinal Cord Lesion, Nursing
Stress (includes vigorous exercise and post-op)
Pregnancy
Chronic Kidney Disease
Drugs (antiemetics, antipsychotics, opiates)

Treatment of Prolactinoma:Medical treatment with dopamine agonists - bromocriptine and cabergoline. Bromocriptine is not well tolerated due to side effects, including orthostasis, nausea and dizziness. Bromocriptine, however, is the choice of treatment in pregnant patients. Nonetheless, both medications can both reduce tumor size and prolactin levels. Pergolide was previously used, but withdrawn due to it's association with valvular disease in patients.

Surgical treatment is done if drug therapy does not help or is poorly tolerated. Still, drugs are usually given post-operatively.

Irradiation is given usually only if the lesion is very large or medical/surgical therapy doesn't help much

Other Pituitary Disorders:

Empty Sella Syndrome - This occurs when the CSF compresses the pituitary. Mostly present in a multiparous women. Can be secondary to irradation or trauma. Sometimes this is benign and does not require treatment, other times hormone replacement is needed.

Pituitary Apoplexy - Infarct and hemorrhage into the pituitary. Patients will present acutely with signs of meningiitis (i.e. meningismus and headache) as well as nausea/vomiting, altered mental status, visual changes and vertigo. If you suspect this, order imaging (MRI is better than CT) and if it is present, neurosurgery needs to be called ASAP! Sometimes steroids are used for minor cases, but patients with severe symptoms need surgical decompression.

Sheehan Syndrome - Postpartum infarct of pituitary with usual decreases in almost all hormones - TSH, ACTH, GH, LH, FSH as well as sometimes causing DI. Hormone replacement is the treatment of choice.

January 15th - LBJ - ASD and Congenital Heart Disease

2010-01-18T08:19:00.000-08:00

Atrial Septal Defects are a commonly tested question on boards, and are a very complicated topic. However, here are the basics you'll need to know for boards.

Even though it is a congenital heart defect, the various types of ASDs can be asymptomatic until adolescence or adulthood. Therefore, physical exam features are clues into the presence of the defect before symptoms develop

In general, patients can present with symptoms attributable to atrial fibrillation, right-sided heart failure, and rarely Pulmonary HTN.

There are 4 types of ASD, each with subtle features to know. You'll most likely be given a patient with an ostium secundum defect, so know this one well. A lot of the concepts are also relevant to the other types of ASD, so just remember what makes the others different (which I'll list)

Ostium Secundum - The most common Type of ASD, and the 2nd most common congenital abnormality in adults (the most common being a bicuspid aortic valve)

Exam: Fixed Split S2 and systolic murmur at LUSB. Loud P2 if patient get Pulmonary HTN
EKG: Right Axis Deviation and RBBB
CXR: Enlarged Right Ventricle, prominent pulmonary vasculature
Diagnosis: Echocardiogram
Treatment: Surgical Closure of the ASD. This is done in symptomatic patients, and in asymptomatic patients that a have pulmonary: system shunt ratio >2:1. If there is pulmonary HTN, surgical closure usually cannot be done, but percutaneous closure can be done.
Complications:Patients can get TIA, Strokes, and Eisenmenger's Syndrome

Ostium Primum
Exam: Pansystolic Murmur of MR or TR
EKG: First Degree AV Block, Left Axis Deviation and RBBB
Treatment: Treatment of choice is percutaneous closure

Sinus Venosus - Know patients have anomalous pulmonary venous return, treat with surgery

Coronary Sinus - Know that patients usually have a Left SVC, treat with surgery

Okay, so what else do you need to know for boards regarding congenital heart disease? Here are the very basic minimums to know about most of the congenital diseases in adults that you will encounter on boards:

PFO:
Diagnose with agitated saline and TTE
Evidence to suggest there is an association b/w PFO and migraines and cryptogenic stroke
Some advocate closure of a PFO in those with cryptogenic stroke, but this is controversial

VSD:
Exam with holosystolic systolic murmur at LLSB, Prolonged Split of S2, as well as murmurs of AR/TR

Diagnose with Echo (suggestive) but need cath to tell difference in O2 Sat b/w Right Atrium and Ventricle

Patients with large VSDs, Significant Shunt, Progressive AR and Volume Overload undergo closure

If left untreated, patients will develop Eisenmenger Syndrome

PDA:
More common in females, may have history of congenital Rubella infection.

Can present with symptoms of heart failure, and can get pulmonary HTN

Exam wth a Machine-like murmur at LUSB. May have bounding peripheral pulses

Interestingly, if Einsenmeger's occurs there is "differential cyanosis" - only in the lower extremities

Diagnose with Echo, Cath can reveal difference in O2 sat b/w Right Ventricle and Pulmonary Artery

Treatment is closure if the patient has symptoms (but not if the patient has with Pulmonary HTN!)

Coarction of Aorta:
Usually associated with Bicuspid Aortic Valve, and patients can get Mitral Valve disease, as well as LVH

Patients can present with HTN, symptoms of CHF and leg claudication

Exam with a delayed pulse between radial/brachial and femoral areas. Femoral Pulse can be absent. HTN can be present in the Upper Extremities compared to Lower Extremities. Patients usually also have a systolic murmur

CXR with Rib Notching (due to collateral vessels) and a "Figure 3 Sign" (dilated aorta above and below coarcted area)

EKG - LVH

Diagnosis - MRI can visualize best, cath usually done to measure degree and gradient

Treatment - Can do balloon with stenting or surgical repair. Usually done in younger patients, or those with an increased gradient

Outcome - patients have risk for aortic dissection and advanced HTN

January 14th - MHH - HOCM/IHSS

2010-01-18T07:15:00.000-08:00

Background: Hypertrophic Cardiomyopathy is inherited about half the time (autosomal dominant). It is these patients with inherited disease that have a high risk of ventricular arrythmias and sudden cardiac death. Annual Mortality in Adults is around 2%

Pathophysiology: Patients can get asymmetrical septal hypertrophy, concentric hypertropy, and other areas of the heart may be involved. Due to this hypertrophy, a narrow outflow tract occurs and there is a pressure gradient that occurs.

Clinical:
Patients can present along the spectrum of disease - syncope, dizziness/presyncope, signs of diastolic dysfunction (dyspnea, PND, orthopnea), myocardial ischemia (angina), palpitations (arrythmias), and sudden cardiac death. However, most are asymptomatic early in the disease course, and remember that sudden cardiac death can be the first clinical feature. The Exam will reveal a mid-systolic murmur in the RUSB that increases with Valsalva. An S4 is usually present. Not uncommonly a double (and sometimes triple) apical impule is felt. Carotid pulse will be brisk, and is sometimes bifid.

EKG and CXR:

Some may have deep T-wave inversions in the inferior and anterior leads of the EKG, some patients may have inferio-lateral Q-waves. Both the EKG and CXR can reveal LVH and LAE.

Diagnosis:
Echocardiogram is diagnostic. There are multiple findings, but a septum that is too thick (and thicker than the posterior wall) is usually present. Outflow tract obstruction is usually seen, as well as abnormal motion of the anterior mitral leaflet. Most patients should have a Holter Placed. Cardiac cath is not usually done on these patients unless surgical intervention is planned.

Treatment:
Beta Blockers are the treatment of choice. These are given to those with a family history of sudden cardiac death, and in patients with symptoms. Long-acting Calcium Channel Blockers are used as well (esp Verapamil). If patient has volume overload, give small doses of diuretics, as patients are preload dependant and low volume is dangerous. If patients have outflow tract obstruction, septal myectomy is performed. Septal ablation with ethanol can also be performed. AICDs are placed in those at high risk for Sudden Cardiac Death. Remember: Avoid aggressive diuresis as well as digoxin and diuretics.

January 11th - LBJ - Polymyositis/Dermatomyositis and Rheum Labs

2010-01-13T08:38:00.000-08:00

Today at LBJ a case of Polymyositis was presented

Here is an overview of the inflammatory myopathies and some rheum labs to know for boards

The 3 Inflammatory Myopathies you should know about for boards are Polymyositis, Dermatomyositis and and Inclusion Body Myositis

Clinical
Polymyositis and Dermatomyositis: Proximal Muscle Weakness. Classically they have difficulty "rising from a chair." Also they can have trouble lifting their head up and trouble climbing stairs.
Pain is not frequently present in these patients (myalgias in less than 30%), it is more muscle weakness. Arthralgias may be present, and pharyngeal weakness can lead to dysphagia/aspiration.
Dermatomyositis is essentially Polymyositis with a rash, but with more to know on this in a bit

Diagnostic Criteria:
1. Symmetrical weakness of limb girdle muscles
2. Muscle Biopsy showing necrosis and perifasicular atrophy
3. Elevated Muscle Enzymes (Can be any - CK, Aldolase, LDH and AST are the most often used)
4. EMG with small action potentials, sharp waves and high frequency discharges

Definite Polymyositis is all 4 above
Definite Dermatomyositis is 3/4 above + Skin/Rash Findings c/w disease

So what are the skin/rash findings... There are many. For boards, you'll need to know:

Gottren's Papules - purple/scaly eruption over the MCPs

Heliotrope Rash - purple discoloration of upper eyelids

Shawl Sign - photosensitive erythema on anterior chest

So, like stated Dermatomyositis is clinically polymyositis with the skin changes.

Workup/Labs:

Your workup for these patients will be what is necessary to help diagnose (i.e EMG).

Muscle biopsy is done, but usually after MRI - so they know where to target the biopsy

CXR should be checked at the time of diagnosis to look for Interstitial Lung Disease

ANA is Positive in >90 of Patients

Anti-Mi2 can be present in Dermatomyositis (<25% of the time)

Anti-Jo1 can be present in Polymyositis - and when this is present patients is known to "antisynthetase antibody syndrome) - characterized by polymyositis, arthritis, interstitial lung disease, fever, Raynaud's and

"mechanics hands" (a dry scaly rash on the fingers)

Other antibodies may be positive if there is an overlap syndrome present (more on this later)

Complications:

- Like stated before, pharyngeal involvement can lead to aspiration

- Patients can get cardiomyopathy or arrythmias from cardiac involvement

- Interstitial lung disease is a complication as well

- Malignancy: not so much a complication, but a disease association. Especially in patients with Dermatomyositis, there is evidence that a workup for malignancy should be done. The most common malignancies found in these patients are ovarian, lung and head/neck. So, a good screening/workup should be done in patients with Dermatomyositis. CT scanning of the Chest, Abdomen and Pelvis are usually done

Treatment:

Initially with High Dose Prednisone (1-2 mg/kg/day) which is continued until elevated enzymes decrease

After these values begin to decrease, the dose is tapered to maintenance of 5-10mg daily. Steroid sparing agents (i.e. MTX or AZA) can be used. Hydroxychloroquine can be used for the skin lesions.

Inclusion Body Myositis:

All you need to know is that this occurs in patients that are older than 50 years, and patients have DISTAL muscle weakness> Proximal weakness. Dyphagia is usually present as well (greater than 50% of patients). Concominant cardiovascular disease is usually present in these patients, but may be due to their age on diagnosis. Muscle Biopsy is diagnostic. Sometimes it is precipitated by drugs such as alcohol and cocaine. To treat, stop offending agent and can give steroids, but they don't help too much.

For Boards, here is a quick Antibody Review For You:
ANA - Positive is so many things.... SLE, Scleroderma, Sjogrens, Mixed Connective Tissue, Myopathies

Anti-Histone - Drug Induced Lupus... Remember these patients have the same clinical findings as in regular Lupus, but the CNS are Renal findings are rare

Anti-CCP - Diagnose/Send in patient with early RA

RF - Rheumatoid Arthritis

Anti-Jo1 - Antisynthesase Syndrome

Anti-Mi2 - Polymyositis

Anti-Smith - Specific Test for SLE. Good to Send for Flare.

Anti-dsDNA - SLE. Good to Send for Flare. Predicts Renal Involvement

Anti-U1 RNP - Mixed Connective Tissue Disease - Patients get SLE + Polymyositis + Scleroderma

SSA (Anti-Ro) and SSB (Anti-LA) - Sjogren's and SLE. SSA with Neonatal Lupus too.

Anti-scl70 - Diffuse Scleroderma

Anti-Centromere - CREST Syndrome (i.e. Limited Scleroderma)

c-ANCA - Wegeners

p-ANCA - Churg-Strauss and microscopic Polyangiitis. These two are also MPO +: know that there are diseases which are p-ANCA positive and MPO Negative (such as ulcerative colitis and hepatitis)

Anti-Mitochondrial - Primary Biliary Cirrhosis

Anti-Smooth Muscle - Autoimmune Hepatitis (patients are usually ANA positive as well)

Reference:
Images Courtesy of
Picasaweb: picasaweb.google.com/.../6sgfojHcfP1D90x2j_2ANw
Emedicine: emedicine.medscape.com/article/332783-overview
mediwire.skyscape.com

January 8th - MHH - Glomerulonephritis

2010-01-12T12:44:00.000-08:00

Today at Hermann, a case of possible GN was presented in a patient with Hepatitis C. Here is a general overview of Glomerulonephritis:

Patients can present with HTN, Oligemia, Hematuria and peripheral edema. If you see dysmorphic RBCs or RBC Casts, think of a glomerular disorder with a nephritic syndrome component

There are multiple ways to memorize the GNs. I like to think of them as those causing low complement and those with normal complement. The ones with low complement you can think of having a "systemic disease" present versus a more renal-based pathology...

Low Complement - Systemic Diseases
SLE - Think when patient has some of the 11 current diagnostic criteria
Endocarditis - In setting of fever and murmur
Cryoglobulinmenia - Patient with underlying Liver Disease, arthralgias and skin rash
Shunt Nephritis - after insertion of vascular shunt
Cholesterol Emboli Syndrome - Post cath/vascular intervention with toe rash/ischemia and eosinophilia

Low Complement - Renal Causes
1) Post-Infectious - Occurs on average 10-14 days after strept infection (including pharyngitis or impetigo) but other infections can cause PIGN as well. If you want to tell for sure that there is prior infection, you can send ASO titers or anti-DNAse B titers. Complements are low, but for no longer than 2 months. Most patients self-recover, but some go on to need dialysis. Treat the underlying infection.

2) Membranoproliferative - Remember this disease can present with a nephrotic overlap in addition to a GN. There are many underlying "triggers" - but Hepatitis C is the most common. Complements stay low for LIFE - unlike with PIGN where they can return to normal after 2 months. Children are usually given steroids, adults have the underlying condition treated (especially IFN for Hepatitis C) and some are give Aspirin as well.

Normal Complement (i.e. the Pauci-Immune diseases)
1) ANCA-associated and other vasculitis
Wegeners: c-ANCA Positive. Granulomas in the Upper Airway, Lung and Kidneys. Consider in a patient with history of sinusitis or recurrent episodes of otitis media. CXR with Lung nodules, cavities or infiltrates.
Arthritis and purpura are common as well.
Churg-Strauss: - p-ANCA positive. History of allergic rhinits or asthma that is difficult to control. High serum eosinophils. Many patients with have arthralgias and neuropathy.
HSP - Arthralgias, palpable purpura, abdominal pain and renal failure. The debate is out whether or not to give these patients steroids, as most patients recover without treatment.
Microscopic Polyangiitis - p-ANCA Positive. Can present with a multitude of symptoms, and often involves the lung. Many patients have fever, palpable purpura, mononeuritis multiplex and arthralgias.

2) GBM Diseases - Essentially those that attack the basement membrabe of both the kidney and lung together. Goodpastures Syndrome is the one to know. Pulmonary hemorrhage with various degrees of hematuria are key. Send anti-GBM antibodies. Treat with repeated plasmapheresis combined with glucocorticosteroids and cyclophosphamide.

3) IgA Nephropathy - More common in males and Asians. Unlike with PIGN, these patients will have GN immediately after the antecedent viral infection. They can have microscopic or gross hematuria, and even extreme exercise can "trigger" the disease. Patients may need ACEI and Fish Oils.

4) Alports - X-Linked with cochlear disease and lens involvement.

Also remember that any of these nephritic syndromes can become RPGN (i.e crescenteric GN) if the creatinine rapidly rises within days to weeks. Those diseases with ANCA positivity and GBM Syndromes are notorious for causing this to occur. Treat the ANCA disorders (and SLE) with steroids + cyclophosphamide. Treat the Anti-GBM diseases with plasmapheresis, followed by steroids + cyclophospamide.

January 7th - LBJ - Delirium

2010-01-12T07:32:00.000-08:00

How do you Diagnose Delirium? With the CAM:
A - Acute Onset and Fluctuating Course
B - Inattention
C - Disorganized thought (rambling speech, changing subjects)
D - Altered Consciousness (from stupor to hyperalert)
(To diagnose Delirium you need A and B plus C or D)

How to differentiate from dementia - Essentially more insidious onset, and patients with dementia usually have normal consciousness.

Risk Factors: Increasing Age, previous history of delirium or cognitive impairment, underlying pain, high dose of pain meds, underlying chronic diseases (i.e. malignancy)

Causes: You name it and it can cause delirium...
I WATCH DEATH is a good mnemonic, but there are many out there:

Infection (UTI, PNA are common, but any cause possible)
Withdrawal (of EtOH or other drugs)
Acute metabolic (renal failure, liver failure, glucose)
Trauma
CNS pathology (you name it, it's here)
Hypoxia (any cause - Embolism, infection, anemia)
Deficiencies (electrolytes)
Endocrinopathies (esp Glucose, Thyroid)
Acute vascular diseases (MI, CVA)
Toxins or drugs (This list is endless - offenders include benzos, quinolones, narcotics, steroids)
Heavy metals

Other Issues That can cause this - HTN, post-op state, seizures, fecal impation and many others....
Treament:
1) Prevention - Frequent reorientation and stimulation (i.e. Lights on during the day/sitter). Maintain the sleep-wake cycle in patients, make sure they can hear well and see well, make sure they get good hydration and nutrition, and don't restrain them ig you can (this includes foleys & SCD/TEDS)
2) Treat the underlying condition (i.e. infection, offending medication, pain)
3) Haloperidol and other antipsychotics may be needed, especially in the post-op state

January 7th - LBJ - TTP

2010-01-12T06:59:00.000-08:00

So, remember that mnemonic in First Aid - "FATRN" - Fever, Anemia, Thrombocytopenia, Renal Failure, Neurologic Changes - Well it's good for med school memorization, but not applicable to TTP in the real world. Remember - before the treatment for TTP was perfected, those patients did have Renal Failure and Altered Mental Status - but we see that not too often now because we treat patients beforehand - if you do see these in a patient it is late stage disease!!

So when do you think of TTP on Boards? Whenever you see the combination of a Microangiopathic Hemolytic Anemia (MAHA) And Thrombocytopenia. What Makes a MAHA? - fibrin deposition that shears the RBC cells causing fragments, ie schistocytes. These patients will have a low haptoglobin and a high LDH with a Normal Coombs Test. However, do not wait for these lab tests to diagnose. As stated before patients can get Neurologic Disease - anywhere from forgetfullness, delerium to seizures. Don't wait for this to diagnose. Renal Failure is late stage. Don't have to have this to diagnose. So the take home:

TTP + MAHA will be TTP (or even HUS) or some other causes listed below...

There are two forms of TTP - idiopathic and acquired. Acquired is usually due to medications - ticlopidine, clopidogrel, cyclosporine, mitomycin C. Almost all patients with TTP regardless of the cause have a deficiency of ADAMTS13 - which usually cleaves vWF. If you can't cleave vWF - you get large aggregates that cause a thrombotic state. ADAMTS13 is not involved in HUS.

So, If you suspect TTP, look for schistocytes on the smear. If there are at least "occasional" on the smear (i.e. more than 2 per hpf) then they are significant. If you see this with thrombocytopenia, consider treatment immediately...

Before treatment was perfected, mortality was >90%. If TTP/HUS is suspected (and you are sure it's not another condition listed below) then treat with plasma exhange. If you can't get the Line or there is no availability to do plasma exchange, then transfuse FFP in the meantime. Some will even give steroids in the interim. No matter what the platelets are, do not transfuse, as you will cause more clotting. Monitor treatment with LDH Levels.

What else can cause Schistocytes (i.e a MAHA) that you need to know for Boards, and how to tell Apart:
TTP: As per this article
HUS: Can present like TTP, more likely in young patients, almost all will have some renal insufficiency
DIC: Will have MAHA and TCP, But PT and PTT are elevated, unlike with TTP/HUS where they are normal
HELLP - MAHA + TTP But Patient will be pregant and have elevated liver enzymes
Malfunctioning Valve Prosthesis: - Usually does NOT cause Thrombocytopenia but will have MAHA. PT and PTT are normal unless there is an underlying disorder or patient is on warfarin for the valve!
Malignant HTN - Can tell by the BP Reading. Also, Thrombocytopenia is uncommon with this

Just a bit more on HUS: There are two forms - in children this is usually triggered by antecedent bacterial enteritis, especially E. Coli. Within a week of the infection, patients can get renal failure, MAHA and TCP. In adults there are forms of HUS after bone marrow transplant and chemotherapy. Sometimes it is hard to distinguish TTP/HUS - so even when HUS is considered, plasma exhange may be used "just in case" TTP is going on.

January 5th - LBJ - Testicular Cancer

2010-01-06T10:18:00.001-08:00

Morning Report Today was a patient with Testicular Lymphoma. Here is some brief board relevant material for testicular cancer. There is a lot in the reading material out there, but for the boards you will not need to know the basics (not the nitty gritty) about staging and treatment, but you must know workup and tumor markers....

Testicular cancer is the most common solid malignancy in adult males under the age of 35. The case presented was testicular lymphoma - essentially for boards, suspect testicular lymphoma with a testicular mass in any man above the age of 45!!! PEARL: If you think a patient has epididymitis, and they fail a course of antibiotics - U/S!!!! - it's cancer!!!!

The vast majority of testicular cancers overall (>95%) are germ cell tumors (i.e. Seminomas and Non-Seminomas, more on this later). Others, such as the aforementioned lymphoma as well as sertoli/leydig are rare. You will not likely be tested on these "other" cancers on boards.

Risk Factors for testicular cancer include cryptoorchism, family history, Klinefelters, and HIV/AIDS. Remember that men with cryptoorchism have increased risk of cancer in BOTH testicles, and the longer you wait to perform orchiopexy, the higher the risk of developing cancer.

Workup:
You should know about workup as well as tumor markers and classification for the boards. If your ultrasound is suggestive of cancer, NEVER NEVER NEVER biopsy. Always do an inguinal orchiectomy with pathology. If you are suspecting testicular cancer on U/S you should order LDH, AFP and hCG. These makers are never used to diagnose (with one exception - mentioned below) and are used for staging and monitoring therapy/relapse.

The Markers:
Seminomas: ALWAYS AFP Negative, can produce hCG, but rarely do so (about 10% secrete hCG)
Non-Seminomas:
    - Teratoma - ALWAYS Negative for BOTH AFP and hCG)
    - Choriocarcinoma - ALWAYS Positive for ONLY hCG)
    - Yolk Sac - ALWAYS Positive for ONLY AFP)
    - Embryonal - ALWAYS Negative for AFP, about half secrete hCG)

The exception - So, the take away from these markers for boards (besides knowing them) from a diagnostic purpose is the classic question - testicular pathology reveals that the cancer is a seminoma, but the AFP is high - well, the pathology is wrong, and there is some non-seminoma component!!!!! Therefore, the patient is treated along the non-seminoma pathway per below...

Staging for both Seminomas and Non-Seminomas: There are pretty involved details, but you'll just need to know the basics for knowing the treatment approach. Know that markers and levels are also used, but you do not need to know the specifics, only this:
Stage I: Testicle Along
Stage II: Retroperitoneal LN involvement
Stage III: Mets

Treatment: When Combo Chemo is Given it's usually either BEP (Bleomycin, Etoposide and Cisplatin) or EP alone.

Seminoma:
Stage I: Orchiectomy alone or combined with surveillence or single agent chemo or radiation. [NOTE: Surveillance is generally only used for patients that have a risk of side effects from radiation... Chemotherapy is sometimes slightly favored over radiation due to the side effect profile of single agent chemo being better than radiation.... so the boards will not ask you which is better, chemo or rads....)]
Stage II: Orchiectomy + Chemo or Orchiectomy + Radiation
Stage III: Orchiectomy + Chemo

Non-Seminoma: Treat based on stage
Stage I: Orchiectomy + Chemo (favored) or Orchiectomy with surgical removal of the LN (I.e. RPLND)
Stage II: Orchiectomy + Chemo or Orchiectomy + RPLND, although most will do Orchiectomy + both Chemo and RPLND
Stage III: Orchiectomy + Chemo

Some info on relapse: If tumor markers rise after Surgery or Radiation - More chemo is given. Be aware that alternative regimens to BEP and EP are used, but you don't need to know them (...so I won't list them!) If patient has a non-seminoma and have masses found on re-imaging - consider teratoma with surgical removal.

Complications: Infertility, so recommend sperm banking prior to Tx
                         Secondary Malignancies, esp AML, from Chemo

Overall, there is a lot of info on testicular tumors that technically can be asked on boards, but like I stated - just know basic workup, markers and some info about treatment options...

January 5th - MHH - Aortic Stenosis

2010-01-06T09:19:00.000-08:00

Today at Morning Report, a case was presented by the cardiology service regarding a consult for a patient with aortic stenosis. Here is a brief overview of the disease for board purposes...

Predisposing conditions: Most common cause is calcific disease of the normal trileaflet valve, but patients with congenital bicuspid valves also get AS. Patients with this congenital condition usually present earlier, usually between ages 40-60, as opposed to those with calcific disease who presents after 60. Rheumatic fever is a cause as well, but rarely without involvement of mitral valves. Also, keep in mind that patients with AS commonly have concurrent coronary artery disease. Patients with Heyde's syndrome, associated with acquired von Willebrand syndrome, can have AV Malformations and GI Bleeds in association with Aortic Stenosis.

Clinical presentation: In the earlier stage of the disease, patients can present with exercise intolerance and fatigue. Remember the triad of Angina, Syncope and LV Failure. These symptoms also portend prognosis, with medical treatment leading to survival rates of about 5 years with angina, 3 years with syncope, and 2 years with LVF.

Physical Exam: The murmur is a harsh mid-late systolic cresendo-decresendo (i.e. "diamond shaped" murmur) at the RUSB or suprasternal notch. It can radiate into the carotids. The carotids develop a slow upstroke. The aortic component of the 2nd heart sound is usually diminished, and as the condition gets worse, A2 can disappear. Also, due to radiation of the murmur, some elderly patients may have the highest intensity at the apex. Overall, the murmur intensity decreases with Valsava and intensifies with squatting. An S4 is usually present, and a click may be present in those with bicuspid valves.

Diagnosis: Doppler is needed, and used to classify based on severity (the valve area is probably all you need to know for boards!). Patients also need repeat TTE's yearly, sometimes more frequently if severe dz present.

Severity   Mean gradient (mm Hg)     Aortic valve area (cm2)
Mild                < 25                                     >1.5
Moderate          25-50                                 1-1.5
Severe              >50                                    <1
Critical            >80                                     <0.5

Treatment:
Medications: Judicious use of diuretics if patient has symptoms of volume overload, but this can cause problems in patients with severe disease. Same with afterload reduction - use carefully. Treat HTN with usual agents. Some studies have shown that "statins" reduce the progression of the disease.

Surgery (i.e. aortic valve replacement) is recommened for:
      -Severe AS with Depressed EF
      -Patients that have symptoms (angina, syncope, NYHA II or greater)
      -Asymptomatic and needs other surgery (i.e. CAGB)

SO... what is aortic sclerosis? Patients with this condition have a thickened valve but without outflow obstruction. Therefore, they are usually asymptomatic - although the murmur findings are very similar to aortic stenosis, so it is hard to distinguish on physical exam.

December 22nd - MHH - Hematuria

2009-12-23T14:18:00.000-08:00

The two cases presented at Morning Report today were related to hematuria - one case is a patient with Acute Promyelocytic Leukemia (APL), the other was one in which the patient had metastatic Renal Cell Carcinoma. See a prior post for details on APL. Here is some information about workup and other details regarding hematuria

Definition: The Prescence of 3 erythryocytes/hpf on a urinalysis that is centrifuged. Some references say that this should be repeated to confirm the presence of RBCs.

Causes: There are many to know, but here is a semi-exhaustive list of the causes.
Nephrolithiasis
Benign Prostatic Hypertrophy
Prostatitis/UTI
Schistosoma haematobium infection
Renal Cell Carcinoma/Ureteral Malignancy/Bladder Carcinoma/Prostate Cancer
Strictures
Coagulopathy (and it's various causes)
Excessive Exercise
Injury/Trauma (including Foley placement)
von Hippel-Lindau disease
Polycystic Kidney Disease
Sickle Cell Disease and Trait
IgA Nephropathy and Thin Basement Membrane Disease
Any of the various causes of glomerulonephritis (i.e. SLE, PIGN, MPGN, Goodpasture's Syndrome, Anti-GBM Disease, Hemolytic Uremic Syndrome etc)

Other things to consider: Remember, some medications (such as rifampin, dilantin and chloroquine) can cause a false positive test for blood on the urine dipstick, but there will be no RBCs. Similarly, remember that in rhabdomyolysis, Blood is reported as +, but RBCs are absent. These should be considered in all cases of hematuria. Some foods cause the urine to turn red with a completely normal urinalysis - including beets, berries and food coloring.

Basic Workup:

All patients with hematuria should have a metabolic panel (to evaluate renal function), CBC and coagulation studies performed.

As far as determining the specific cause, one should first do a Urinalysis with microscopy to determine if there is a glomerular vs nonglomerular cause. Remember that glomerular causes will have RBCs casts and/or dysmorphic Red Blood Cells. If there is indeed a glomerular cause, then workup includes determining the amount and quantity of protein present. Some will then send serum complements (esp C3) to divide the causes into those with normal and those with low Complement levels. Without an evident cause based on the serum workup, renal biopsy may be necessary for the glomerular causes.

If the clinical history is suggestive of infection, then urine culture can be sent. However, some causes of a positive urine culture must be considered in this category besides UTI (i.e. prostatitis, PCKD, and some malignancies!)

If the clinical history is suggestive of nephrolithiasis, one can do a helical CT scan.

If the patient has risk factors for bladder malignancy (i.e. Age>50, smoking history, pelvic irradiation, analgesic abuse) - cystoscopy is warranted as the next step. Urologists actually like three studies done - Urine Cytology, Cystoscopy and CT imaging of the abdomen/pelvis.

December 21st - LBJ - Colorectal Carcinoma/Familial Cancer Syndromes

2009-12-21T11:29:00.000-08:00

Today at LBJ morning report our first case was of a 37 year old African American Male with Rectal Carcinoma and multiple polyps on colonoscopy. Also, he had multiple hyperpigmented macules scattered throughout his body. This brings up a good point to discuss the various inherited colorectal cancer syndromes that you'll need to know for boards. All together these inherited syndromes are responsible for approximately 10% of cases of Colorectal Cancer in the US (the other 90% are from sporadic polyp formation)

Familial Adenomatous Polyposis (FAP):

-Most cases are autosomal dominant, and result from a mutation in the APC gene on Chromosome 5

-By the age of 14-15 patients start developing polyps throughout the colon, and most patients get colorectal cancer from these polyps by the age of 35-40. At this time, in most patients, thousands of polyps are present in the colon. There is a form of FAP that is inherited in an AR fashion, and they have less polyps by this age- only in the hundreds

- Patients also get desmoid tumors scattered thoughout their GI tract - leading to obstructive/compressive symptoms.
- Cancer of the ampulla of Vater occurs in about 10% of patients. Other malignancies seen
in patients with FAP include thyroid, pancreatic and gastric cancer.

- Another finding is retinal epithelial hyperpigmentation. (This is a favorite one-liner for
    boards!)
- Patients need surveillance sigmoidoscopy/colonoscopy starting at age 10-12, and most
   patients undergo prophylactic colectomy by the age of 30.
- All Patients need Genetic Counseling and screening. Surveillance
   EGDs and thyroid U/S are recommended

Variants of FAP:

Gardner's Syndrome - Skull/Mandible Osteomas, Supernumary Teeth, Epidermoid Cysts and/or Lipomas along with polyps/colorectal cancer. + high incidence of retinal epithelial hyperpigmentation. (and a picture of what epidermoid cysts look like to the left)

Turcot's Syndrome - Polyps/Colorectal Cancer combined with CNS Dz (esp meduloblastoma/glioblastoma)

Lynch Syndrome/Hereditary Non-Polyposis Coli Syndrome

Autosomal Dominant Inheritance. Patients have about an 80% lifetime risk of developing colorectal cancer. 2/3rds of colorectal cancers occur in the region proximal to the splenic flexure (unlike most malignancies in the US - which are predominantly left-Sided) Patients develop colon cancer in their 40's. Other malignancies seen in patients with HNPCC include ovarian, endometrial, gastric and a slew of other rare cancers.

The most recent Amsterdam Criteria establishes the guidelines for suspicion/diagnosis of HNPCC:
One or more of the HNPCC-related cancers diagnosed younger than 50 years
Two successive affected generations
Three or more family members with HNPCC-related cancers

So if your patient fits this criteria, or has synchronous or metachronous colorectal cancer along with any other cancer that is seen in patients with HNPCC - be suspicious that this is occuring!!!

Family members need to be screened, and they have to get colonoscopies starting at age 25. Females get aggressive screening for endometrial cancer, and some clinicians send CA-125 regularly.

Peutz-Jehgers Syndrome

This is more of a disease of "adolescents", but just to know because it is fair game on the boards:

- Hyperpigmented macules on the lips/mucosa

- Multiple hamartomatous polyps in the small intestine, large
intestine and stomach. These have low malignancy
potential, and usually causes symptoms such as
hematochezia and even intussusception

- Patients still have an overall increased risk of colorectal
adenocarcinoma, and other malignancies such as
breast, gastric, pancreatic, lung, and many others.

December 18th - LBJ - AML and Quick Leukemia Info

2009-12-18T13:59:00.000-08:00

Today at LBJ a case of AML was presented. Here is some more detailed info about AML, all you'll need for boards...

We see the leukemias very often in morning report, so I will post more details on other leukemias as we have cases in MR.

However, from a clinical/ board recognition standpoint - I have put the salient clinical and lab features of the other leukemias. Especially the labs! This is how you can tell on boards, clinically and in MR which is which!!!

AML
Epidemiology: By far, the majority of acute leukemias are AML (>80%)

Risk Factors: Radiation Exposure, Chemotherapy, Benzene Exposure, Genetic Diseases (i.e. Downs, Bloom Syndrome) and Preexisting Heme Diseases such as MDS, Myeloproliferative disorders, PNH

Patients present with: Constitutional symptoms, bone/testicular pain, gum infiltration, splenomegaly, LAD
NOTE: Since platelets and hemoglobin are usually decreased on diagnosis - patients can present with these findings (i.e. pallor, fatigue and petechiae) Also, a leukostasis syndrome can be present in patients with WBC Counts that are >100,000: Hypoxia, pulmonary infiltrates, retinal hemorrhage, priapism, CVA, Myocardial infarction, etc.

Labs/Workup:

Patients with AML on presentation are invariably anemic and thrombocytopenic. Most patients will actually have severe thrombocytopenia (<50,000). So what about the white count?? Well, it can be down, slightly elevated or very high. So AML can have pancytopenia OR a modest to very high WBC count with anemia and thromboctyopenia. Remember This!!!!

The Blood Smear/Differential will have >20 Blasts in most cases. The Auer rod is diagnostic that the cell line is myeloid in nature (see picture!)

and represents AML. Heme Path docs can tell this is the case by special stains.

Bone Marrow is done for cytogenetics in order to tell prognosis, and to guide treatment. Favorable types include t(15;17), t(8;21) and inv(16). Poor cytogenetic profiles include inv(3), del 5 and del 7

There are 8 subtypes of AML by the WHO - you'll probably have to only know about acute promyelocytic leukemia - M3 - has translocation (15;17) - can present with DIC. Treat with high dose ATRA (all trans-retinoic acid)

Treatment:
The patient undergoes "Induction" and "Consolidation" in a "7" + "3" method
Induction: Given 7 days of IV Cytarabine (Ara-C) plus 3 days of bolus Anthracysline (Idarubicin or Daunorubicin are used) - after this induction, patient will be severely pancytopenic.
Then the consolidation phase: Patients are usually given either high dose Ara-C or undergo Bone Marrow Transplant at this stage. Allogeneic Bone Marrow Transplant or Autologous stem cell transplant is usually reserved for patients with high-risk/poor prognostic cytogenetics.

Treatment of patients with the leukostasis syndrome is with hydroxyurea and/or leukopheresis

CLL: Patients are usually asymptomatic at time of diagnosis. Constitutional symptoms are rare. 1/3rd will have significant LAD and/or organomegaly. Some patients may have signs/symptoms of anemia.
Labs with CLL: Patients usually have modestly elevated WBC counts. Patients will usually be anemic. The WBC Count Rarely gets highly elevated (i.e. >30,000) and Thrombocytopenia is uncommon.
Smear with mature lymphocytes and smudge cells.

CML: Patients can present exactly like CLL - meaning they rarely have constitutional symptoms. Lymphadenopathy is RARE with CML (as compared to CLL) but patients usually have organomegaly (especially splenomegaly). In fact, abdominal pain/fullness or early satiety are the common presenting symptoms (both on boards and I've seen in patients) due to splenomegaly. They can also have a leukostasis syndrome like in AML, but this is rare unless the blast count is very high. Remember that CML is a MYELOPROLIFERATIVE Disorder. That being said: The WBC count is always high. This is always the case. The Hemoglobin can be low, normal or high. The platelet count is either normal or high.
Smear with immature cells - promyelocytes, metamyelocyes and myelocytes. Patients can have increased basophils and/or eosinophils as well.

ALL: Rare in adults compared to other leukemias. What you'll need to know, for the most part - can present just like AML - lymphadenopathy, organomegaly, etc. Can also get leukostasis syndrome as the WBC count can get very high.... but can also have a low WBC count. Just like AML: Pancytopenia OR a modest to very high WBC count with anemia and thromboctyopenia. However, since it is a disease of lymphoid lineage - unlike AML - the smear will show predominantly lymphoblasts.

December 15th - MHH - Pulmonary Carcinoid

2009-12-16T09:11:00.000-08:00

Today at MHH morning report a case of pulmonary carcinoid was presented.

For quick board-type "pointers, " here are some key Learning Points about carcinoid in general:

Locations/Sites:
Most commonly affected areas are the GI Tract (especially Stomach, Small Intestine, appendix and rectal) and the Bronchial location. Other sites involved, although rare, include ovaries, pancreas, gallbladder and testes

Symptoms:
For Pulmonary Lesions:
1) Local Effect - Obstruction, persistant pneumonia, atelectasis, bleeding from irritation,
     dyspnea, wheezing

2) Systemic -
     -About 15% get the "carcinoid syndrome": Diarrhea, Flushing, Tachycardia,
       Bronchoconstriction, hemodynamic instability - all from excess serotonin. Since these are
       excreted directly into the systemic circulation, patients do NOT have to have metastatic
       disease to the liver to get this syndrome.
     -The flushing usually is on the upper torso and face and lasts 10-30 minutes
     -Episodes of Diarrhea can number even >15x a day
     -Patients can get tricuspid and pulmonary disease (esp stenosis) due to fibrosis caused by
       serotonin. The other valves are not affected because the lungs degrade serotonin
     -Patients can also get a secondary pellagra from niacin deficiency
     -Wheezing and asthma are present in >25% of patients
     -About 1% get Cushings Syndrome from ectopic ACTH production

For GI Lesions:
1) Local - Anemia, abdominal pain, weight loss
2) Systemic - The carcinoid syndrome as above can occur, but lesions from the GI tract have
     to metastasize to the liver before getting this constellation of findings.

Diagnosis of Carcinoid:
1) Urine 5-Hydroxyindoleacetic acid (5-HIAA) - A metabolite of serotonin. Elevated in 75% of patients.The patient has to be on a strict diet, as certain foods (like caffeine, wine, cheese) can falsely elevate the results. In addition, medications like INH and Acetaminophen can also elevate the results.

2) Serum Chromogranin A is elevated in 90% of patients, but only suggests that a neuroendocrine tumor is present

3) Radionucleotide scan with Indium-111 scan has a high sensitivity and specificity to help localize the lesion

4) For Pulmonary Tumors - Imaging will show a lesion in greater than 75% of patients - Then need Biopsy. Same for GI Tract - can image with colonoscopy (rectal lesions) or CT to better visualize other locations. Then biopsy

Treatment:
Subcutaneous Octreotide helps relieve the symptoms of the carcinoid syndrome in all tumor types.

Pulmonary Carcinoid is usually treated with surgery +/- Chemotherapy with Streptozotocin/5-FU

GI Carcinoids are also treated with surgery, and various chemotherapy regimens are used

December 15th - LBJ - Ascites

2009-12-15T15:14:00.000-08:00

Our Second Case at LBJ Today was a patient with 3-4 weeks of abdominal distention (in this case, ascites). The diagnosis ending up being Alcoholic Hepatitis/Cirrhosis.

Just as a review, an Approach to a patient with ascites includes a differentiation based on the serum Albumin-Ascitic Gradient. This has a published accuracy of >97%!

If >1.1 - Consider Liver Disease/Portal Hypertension.
This can be broken into causes based on location:

Pre-Hepatic Causes
Portal Vein Thrombosis
Schistosomiasis (in Egypt!)

Intrahepatic Causes (i.e "Cirrhosis)
Alcohol Abuse
Viral Hepatitis
NASH/NAFLD (i.e. obesity, dyslipidemia, insulin resistance)

Post-Hepatic Causes (i.e. "Congestion")
Constrictive Pericarditis
Budd-Chiari Syndrome
Tricupsid Regurgitation
Right-Sided CHF

If <1.1: Think Low-Albumin States and non-portal hypertensive causes:
Nephrotic Syndrome
Malabsorption/Protein-Losing Enteropathy
Infectious Peritonitis (TB and some fungal diseases)
Malignancy (Peritoneal Carcinomatosis, Ovarian Cancer, HCC, Psedomyxoma peritonii)
Hypothyroidism

All you'll ever need to know about Ascites actually comes from the AASLD - it includes where to do your paracentesis, how to analyze fluid (including SBP and variants) and treatment:
AASLD Practice Guidelines for Cirrhosis and Ascites

December 15th - LBJ - Young Blebs

2009-12-15T14:30:00.000-08:00

Of Blebs and Bullae

Today at LBJ a case was presented of a previously healthy 33 year old African American Male who presented to the ER with dyspnea. He was found to have a large left-sided pleural effusion, was given IV azithromycin by the ED, and left Against Medical Advice. He was readmitted to the medicine service with the same chief complaint - imaging revealed this large pleural effusion and multiple bullae located in various portions of the lung. He did have a smoking history, but no history of chronic lung disease or prior pulmonary pathology.

These are some of the various causes of bullous disease in young patients:
1) "Normal" - The journal Chest published a review that 6% of healthy young adults can have bullous disease adjacent to the pleura - usually in those with low BMIs that have a positive smoking history.   This was postulated to be due to reduced pleural adipose tissue.

2) Connective Tissue Diseases - Marfan's Syndrome and Ehlers-Danos Syndrome are the most common in the literature.

3) Chronic Cocaine and Marijuana use - both have been linked to formation of bullae

4) Alpha-1-antitrypsin deficiency - Panacinar involvement and usually involves the lower lobes more than the upper lobes. Emphysema usually develops in smokers around the age of 40, and in non-smokers in the mid 50s. Depending on the genetic mutation, however, some patients can have emphysema by the age of 30.

5) Sarcoidosis - Bullous disease can occur anytime during the course of the disease, and is sometimes a presenting finding or can precede the diagnosis by years.

6) Pulmonary Langerhans Cell Histiocytosis - An Interstitial lung disease found almost exclusively in young male smokers. Patients can have constitutional symptoms, or present with cough/dyspnea. The bullae are usually upper-lobe predominant, and 25% of patients develop spontaneous pneumothorax. Interestingly, 10-15% of patients are completely asymptomatic and the disease is found during "other reasons" to do lung imaging. 15% of patients have "extrapulmonary" involvement including bone pain from cysts, diabetes inspidus or rash. Pulmonary cysts are usually visualized on CT Scans. Soking cessation usually leads to resolution of symptoms, although some patients are treated with corticosteroids.

7) Lymphangioleiomyomatosis (LAM) affects pre-menopausal females. Patients have multiple thin-walled cysts, lymphadenopathy, diffuse interstitial infiltrates and eventual fibrosis. They also have a tendancy to form recurrent chylous pleural effusions. There is a disease association with angiomyolipomas and tuberous sclerosis. Patients with LAM are instructed to prevent pregnancy or not take estrogens, as there is evidence that hormones play a role in the pathogenesis of the disease. Treatment involves general care and relieving symptoms of effusions. Some patients are put on bronchodilators. Some have used medroxyprogesterone in the past - but the evidence supporting its use is lacking. Experimental agents, such as chemotherapeutic drugs, are being investigated. Some patients may need lung transplant.

Of note: Centriacinar emphysema is the "classic" pattern seen in smokers, and predominantly affects the upper lobes. There is also a more rare variant called distal acinar emphysema/paraseptal emphysema which causes scattered bullous disease without airflow obstruction. However, it would be RARE in a 33 year old - as it takes at least 20 cigarettes a day for 20 years to form the changes of chronic lung disease.

Some "board review" notes on pleural fluid (as the patient as a pleural effusion)

Light's Criteria (any of these present = exudate)
1. Pleural fluid protein/serum protein >0.5
2. Pleural fluid LDH/serum LDH > 0.6
3. Pleural fluid LDH > 2/3 upper limit of normal

Chest did an analysis of pleural fluid and found that any of the following characteristics are also consistent with "exudates":
1.Pleural fluid protein >2.9 g/dL
2.Pleural fluid cholesterol > 45 mg/dL
3.Pleural fluid LDH > 60 percent of upper limit for serum

Causes of Transudative Effusions:
Congestive Heart Failure (usually bilateral and small, but can be unilateral)
Cirrhosis
Nephrotic Syndrome
Pancreatitis (left sided)
Pulmonary Embolism

Causes of Exudative Effustions
Malignancy (Lung, Breast and Lymphoma)
Mesothelioma (usually bloody fluid)
Infectious (both bacterial and viral)
Esophageal perforation
Pulmonary Embolism
Rheumatic diseases (Rheumatoid arthritis, SLE)
Transudative causes that turn exudative secondary to diuresis
    (This occurs in less than 20% of these patients - to be sure/better classify - if the difference between serum protein and the pleural fluid protein is greater than 3.1 g/dL - the effusion is transudative. Alternatively, a serum albumin-effusion albumin gradient greater than 1.2 g/dL is also suggestive that effusion is most likely a true transudate)

Other notes:
WBC >10,000 = parapneumonic
WBC >100,000 = empyema (this will be obvious as the fluid will be purulent)
High Eosinophil Count (10% of total) = Mesothelioma, parasites/fungal and drug reaction
High Lymphocye Count (>50% of total) = Malignancy or TB
High Amylase - Esophageal Rupture and sometimes malignancy
Glucose <60 = Malignancy or Infection. An even lower glucose can be see with rheum Dx
pH<7.2 (when collected quickly) - can see with infection and some malignant cases. When
       seen in the face of infection, it is an indication for chest tube drainage
Pleural Fluid ADA>45 has a PPV of about 80%
High ANA Titers (>1:160) - SLE and drug-induced Lupus
TG>115 = chylous effusions (can be caused by cancer!)