30 June - Orientation Reference

Welcome, welcome!

During orientation, Dr. Rasnake mentioned a reference for practice called the "Checklist Manifesto" by Atul Gawande. This is an excellent book! The same author wrote a piece for the New Yorker entitled The Checklist in 2007 which contains many of the highlights and thoughts which were the basis for the book.

Here is the weblink:
http://www.newyorker.com/reporting/2007/12/10/071210fa_fact_gawande

21 June - recurrent vesicular rash

Teaching rounds today - 32 y/o female with several medical problems, to include celiac disease (? Dx) and a history of recurrent vesicular lesions on her forehead diagnosed as zoster.

The differential diagnosis of vesicular rash includes a variety of infectious and noninfectious causes - some benign and some potentially fatal.  Varicella, HSV, vaccinia virus, variola virus, enterovirus, rickettsialpox, impetigo, dermatitis herpetiformis, phytodermatitis, and phytophotodermatitis all need to be considered in the correct clinical setting.

Scraping of the vesicle base to obtain cells for DFA is my preferred method for rapid HSV diagnosis, and probes are available for HSV1, HSV2, and VZV.  This article has a summary of the collection procedure as well as other diagnostic methods for herpes virus infections.

Yes, phytophotodermatitis exists - so beware all those mojitos, gin&tonics, coronas, margaritas, and any other lime containing beverage out in the sun this summer.

One recent case in the ID literature emphasizes the importance of making a definite diagnosis - Kaposi varicelliform eruption - generalized vesicular rash that mimics chickenpox but is caused by HSV or coxsackie virus.  Pts with a history of eczema are at significant risk for this.

18 June - Myoclonus

87 y/o female admitted with episodic myoclonus.  She had an underlying history of dementia, Alzheimer's type on treatment with memanting and several other medications.  Her symptoms were rhythmic movements of the bilateral upper extremities and neck muscles.

Pearls:

Myoclonus can occur as part of the natural progression of Alzheimer's, but if it is early and pronounced other diagnoses such as CJD should be considered.

Certain medications (including memantine) can cause myoclonus when drug levels become high.

Clonazepam is an effective intervention for myoclonic symptoms.

17 June - ITP

Today's case was a college student that has been followed for thrombocytopenia for ~ 1 year now.  His initial presentation was with a brief illness with subjective fevers and diarrhea and a transient, possibly petechial rash.  No bleeding occured.  CBC at student health revealed a PLT count of 23K.  He was admitted for workup and observation and was noted to have a prompt increase in PLT count (>50K at discharge).  Peripheral smear was unremarkable, HIV serology was negative, and overall clinical status was good.  He was diagnosed with ITP and discharged.  Over the following year his PLT count has fluctuated but never normalized.  He underwent bone marrow biopsy which was unremarkable.  He has had no bleeding events.

The ASH Image Bank has a complete case presentation with several representative images.  Nice review of clinical aspects of the topic.  Note the large platelet in the center of this image.

Pearls:

ITP is a diagnosis of exclusion - rule out TTP, leukemia, MDS, sepsis, etc.

ITP = immune thrombocytopenic purpura, not necessarily idiopathic...

There was a recently published international concensus statement on the w/u and management of ITP - published in: Blood, Vol. 115, Issue 2, 168-186, January 14, 2010

Some pearls:

Recommended testing for all adult patients includes peripheral smear, coombs test, Rh type, and serology for HCV, HIV, and H pylori. (I guess only infections that start with H cause ITP?)

Treatment rarely indicated for PLT counts >50K and no bleeding
First line therapy: anti-D immune globulin, steroids, and IVIG
Second line therapy: azathioprine, cyclosporine, cytoxan, vincristine, danazol, dapsone, rituxan, splenectomy
Salvage Therapy:  TPO receptor agonists, campath, chemo, HSCT

16 Jun - Hypertrophic Cardiomyopathy and Abnormal Vaginal Bleeding

Coindidenatl admission with abnormal uterine bleeding and newly diagnosed hypertrophic cardiomyopathy.  Probably unrelated?  Possibly not - this study describes functional vWF deficiency in patients with HCM and associated spontaneous bleeding events.  Hmm.

Hypertrophic cardiomyopathy is reviewed in this JAMA article.  Myosin heavy chain, troponin T, and myosin binding proteins are all described to be mutated in HCM - mode of inheritance is autosomal dominant.  This patient presented with evidence of LVOT obstruction, but only 25% of HCM patients have obstructive physiology.  Given this, murmur may be absent in the majority of patients with this disease.  To better differentiate the HCM murmur from other systolic murmurs, some maneuvers can be attempted (in general, things that decrease LV filling will increase HCM murmur):

Valsalva: increases HCM
Standing: increases HCM
Hand Grip: decreases HCM

Found this neat quiz for working up murmurs online - answers are in the back.

Management consists of preventing sudden cardiac death in high risk individuals, treatment of heart failure symptoms (possibly surgical myomectomy) and management of A-fib which is a common comorbid comdition.

With regards to the abnormal menstrual bleeding in this case, one should be aware of the basics of a primary care approach to this condition.  First - rule out pregnancy.  Second - screen by hx and exam for signs or symptoms consistent with PCOS, other hormone disorders, or bleeding disorders like vWF deficiency.  Any uterine bleeding in a postmenopausal woman should worry you for endometrial carcinoma.

14 June COPD

Teaching rounds today reviewed current data regarding treatment of COPD.  The case discussed was a patient who had been admitted for the first time with a COPD exacerbation.  Several recent studies have better defined the role of various treatments for this common and debilitating condition.

First: smoking cessation and long term oxygen therapy (when appropriate) remain the most beneficial treatments available. 

Second: tiotropium appears to be superior to ipratropium and has been shown to decrease mortality.

Third: antimicrobial therapy is beneficial in patients with moderate to severe exacerbations of COPD.  In general, having 2/3 or 3/3 of the following critieria indicate a moderate or severe exacerbations: increased sputum volume, increased sputum purulence, and increased dyspnea.

Fourth: Benefits of inhaled steroids are less clear for COPD, and when used should be limited to those with moderate to severe disease only.

The ACP In the Clinic series recently reviewed COPD and this article is a quick read that highlights the state of the art in COPD management.

11 Jun - Guillain-Barre syndrome

This AMs case was a 40ish year old man admitted with 4 days of progressive ascending weakness with paresthesias.  Mental status was normal.  He had a recent illness with low grade fevers and myalgias but no other significant symptoms or rashes.  He did have a tick bite about two weeks prior to onset, but did not have any attached ticks at time of admission.  Significant flaccid paralysis of the arms and legs was present and reflexes were absent.  No cranial nerve defects were evident.  He rapidly developed respiratory insufficiency requiring intubation.  CSF evaluation revealed significantly elevated protein and a clinical diagnosis of GBS was made.  He has been treated for ~8 days, initially with IVIG and subsequently plasmapheresis but is still ventilator dependent.

Differential for acute flaccid paralysis includes GBS, myasthenia gravis, botulism, tick paralysis, toxins, polio, non polio enteroviruses, and hypokalemia.  The review article linked here has a nice table that helps differentiate clinical symptoms.

A recent review of GBS is in this issue of the BMJ.

Treatment cosists of observation for mild cases, IVIG or plasmapheresis for moderate to severe.  Plasmapheresis has been shown to be effective vs placebo in clinical trials, and IVIG has been shown to be equivalent to plasmapheresis but has not been compared directly to placebo.

Pearls:

You must measure NIF and/or vital capacity - ABG and O2 sats are usually normal right up until total respiratory failure occurs

Autonomic instability (tachycardia, hypertension) is common.

Elevated CSF WBCs should make you consider an alternate diagnosis.

10 June - Acetaminophen poisoning

This AMs case was a 30ish year old female who had been injured in a car crash approximately 2 weeks prior to admission.   On this occasion she was admitted with significant nausea, vomiting, and abdominal pain.  She had a history of heavy alcohol consumption for several years prior to admit.  In the three days leading to this admission she had taken over 30 acetaminophen tablets (dose unspecified).  On admit her transaminases were elevated >2000, her INR was 1.7, and the bilirubin was 3.  There was no evidence of encephalopathy.  Her admit acetaminophen level was 0.9.

Pearls:

Acetaminophen toxicity occurs when liver sores of glutathione are depleted and the toxic metabolite NAPQI accumulates.  Administration of N-acetyl cysteine (NAC) replenishes glutathione and allows clearance of NAPQI.  Alcohol consumption is a well established risk factor for more severe toxicity.

The Rumack-Matthew nomogram helps predict when toxicity will occur, but this nomogram is only valid for single large ingestions with a known time.  Ingestion of multiple doses over several days or ingestion of extended release formulations can provide misleading results.  Also watch your units - confusing micrograms/ml with micromoles/ml when plotting on the nomogram will throw you off significantly!

Ideally, NAC should be given before the LFTs are elevated to be effective.  Not all poison control centers recommend its use once the acetaminophen level has dropped <20 or is undetectable.  This article from NEJM calls this into question.  They recommend more liberal use of NAC, especially when LFTs are elevated.  They refer to 2 studies that show reductions in mortality on the order of 20% in the setting of fulminant liver failure when intravenous NAC is used.  The cost of NAC is modest - only $50 for a full 72 hour treatment course. 

The FDA has taken steps to relable acetaminophen, remove higher dose formilations from the OTC market, and eliminate drugs such as Vicodin and Percocet that have combinations of high dose acetaminophen and opioids.  They have yet to set formal recommendations for max dosage, but anticipate doses of 3.25 grams for healthy individuals and <2.5 grams or outright avoidance for those who consume ETOH or have liver disease. 

9 June - Hyperparathyroidism

This morniongs case was a quite unusual presentation.  A 28 y/o male was admitted with complaints of dysphagia and odynophagia and had had some concomitant symptoms of headache and photophobia.  He had some neck swelling on examination.  Serum chemistries revealed an unexpected finding of hypercalcemia (Ca >13).  PTH was measured at over 900.  Sestamibi scan revealed significant uptake in the R inferior parathyroid area.

Imortant to differentiate parathyroid carcinoma (rare) from parathyroid adenoma (common).  Features that suggest carcinoma in this case include young age, very high calcium (usually 12 or less with adenoma) and markedly elevated PTH (usually only mildly elevated with adenoma).  This article is a comprehensive review of this rare condition. 

Remember to check PTH on patients with even marginal elevations of serum calcium.  If the PTH is not maximally supressed then you are dealing with hyperparathyroidism.  Undetectable PTH in the setting of hypercalcemia has a more broad differential.  In these cases a search for more rare causes of hypercalcemia can be considered. 

Other pearls from this AM:

Elevated alk phos with normal calcium, phosphate, and LFTs suggests Pagets

Hypercalcemia can cause a short QT interval primarily through shortening of the ST segment.  This can produce findings worrisome for early repolarization vs ST elevation and apparently can mimic MI.

7 June - Anticoagulation in the Elderly

In which patients can warfarin be safely resumed after a major GI hemorrhage?  Multiple factors must be considered:  what is the risk of not anticoagulating?  Prosthetic mitral valves may not be forgiving, but a minor DVT several months ago may not pose much risk.  How many CHADS2 points does the A-fib patient have?  How significant was the bleed?  Did it occur at therapeutic INR levels or only at significantly elevated ones?  No simple algorithm for this, but these guidelines from the ACC/AHA give some pointers.

At least with regards to elderly patients with A-fib, physicians tend to overestimate the risk and clinical impact of gastrointestinal hemorrhage or hemorrhagic stroke and underestimate the benefit of anticoagulant therapy. Annals of Pharmacotherapy on Medscape reviews warfarin in the elderly in detail.

Here is a nice review of the literature that largely focuses on antiplatelet therapy in patients with a history of GI hemorrhage.  Key points:  Clopidogrel has lower bleeding risk than ASA, but not by much.  ASA plus PPI has significantly lower bleeding risk than clopidogrel.  Clopidogrel is not as active when given with omeprazole, but other PPIs do not seem to exhibit this effect.

2 Jun MR

Today's case was a patient that was admitted with orbital cellulitis.  He had been treated for an eye infection - "pink eye" per his report, with two oral abx for 2 weeks without response.  Significant proptosis was present on the left.  He was an ESRD patient on dialysis with poorly controlled diabetes.  CT revealed significant orbiral cellulitis with bony erosions.  On admission he did not appear to have necrosis or eschar in the oral cavity or nares and he was treated with vancomycin, zosyn, and cipro.  At surgery however he was found to have eschar in the sinuses and pathology revealed aseptate hyphae consistent with mucormycosis.

This NEJM case has lots of similar to this feature, and breaks down fungal sinusitis into acute, subacute, and chronic.  This patent likely fit into the subacute category.

Pearls: 
Bad DKA with rapidly progressive rhinocerebral infection.  Look for eschar and necrosis.

To differentiate orbital cellulitis from preseptal cellulitis you must evaluate for proptosis.  Physical exam is helpful, measurement with a proptometer is better, and CT imaging with orbit protocol is best. 

Mucormycosis is a group of fungal infections (Mucor, Rhizopus, Absidia, others) that produce rapidly developing infections in immunosuppressed hosts (marrow transplant, AML, DKA, high dose steroids).  The only effective antifungal options for thse infections are amphotericin B and posaconazole.

Rapid consultation of ophtho and ENT/facial plastics is key to preserving vision in orbital cellulitis.  Blindness may occur abruptly and is typically not reversible.  Orbital decompression will allow time for antibiotic therapy to be effective in cases of bacterial infection, but invasive fungal disease usualy requires significant debridement.