Asthma in inpatients

Acute asthma exacerbations are relatively common internal medicine referrals. Some points on managing this potentially life-threatening condition:

Indicators of severity:

Clinical- SILENT CHEST, pulsus paradoxus, acc muscle use, diaphoresis, inability to speak
Peak flow- less than 200 or less than 50% of baseline is severe attack
ABG- hypoxia is rare, and indicates very severe. Hypercapnia or even normal PCO2 is bad; indicates tiring.
CXR- unhelpful usually; may do to exclude pneumothorax (possible complication), pneumonia.

Very important to get a peak flow reading on presentation and then monitor closely q1-2h during therapy to assess progress.

Therapy

1) B-agonist: Mainstay of therapy
Salbutamol 4-6 puffs q1-2h iniitally. Outcomes with inhaler vs. nebulizer are essentially equal assuming proper technique. 1 NEB treatment generally equals 4-6 MDI puffs with a spacer.

2) Ipratroprium: Added if not initially responding or if severe.
Especially recommended for pts with COPD or B-Bl triggered asthma.
Ipratroprium 500mcg NEB q6-8h (can be given with 1st ventolin neb treatment) or MDI 2 puffs of 17mcg each q6h.

3) Steroids:
Consider if:
1) less than 10% increase in PF after 1st dose of B-ag
2) attack in pt on oral steroids before attack
3) PF less than 70% predicted after 1h of treatment
Only difference between PO and IV steroids is onset of action; within 1d for IV vs possibly 2d for PO. Otherwise equivalent. Dose of steroid is not clear. For severe, a commonly studied dose is Solumedrol 125mg IV q6h x 3d. For less severe, consider Solumedrol 30mg IV q8h x 3d then switch to oral.
PO: Prednisone 1-2mg/kg/d divided q 8-12h for 2-4d, then reduce. All pts who received steroids should get oral steroids on discharge; usually prednisone on tapering regimen for 8-10d, but also acceptable if steroid naive to keep on prednisone for 1 week, reassess, and d/c abruptly if less than 10d

4) MgSO4: Some evidence of benefit; blocks SM contraction. 2g IV over 20min. Little toxicity to this dose

5) Epinephrine: last resort; patient will probably need intubation.

6) Final step is rapid sequence induction and intubation by the most skilled person available (there may only be 1 chance), and initiation of inhaled anesthetics (which are bronchodilators). Ketamine is also a bronchodilator.

Little or no role for antibiotics, theophylline, montelukast

Consider admission if:
-peak flow less than 40% of predicted after bronchodilators or less than 25% on arrival
-any hypoxia, distress, etc.

Consider ICU or intubation if:
-Clinically tiring or in respiratory distress
-Hypercapnea or hypoxia
-Worsening on therapy
-PF less than 150

Links:

Click here for acute exacerbation guidelines from 2007

Click here for evidence for magnesium in acute exacerbation

Asthma in outpatients

We had a clerk teaching session on asthma, and I thought I would share some points with everyone:

Diagnosis

Relative increase in FEV1 of 12% post-bronchodil AND over 200cc change. More sensitive test is methylcholine challenge

Steps for therapy: With each, patient education, environmental control

1) SABA prn
2) low dose ICS
3) (low dose ICS + LABA) or medium dose ICS
4) medium dose ICS + LABA
5) high dose ICS + LABA and consider omalizumab for allergic asthma (eosinophilia or symptoms)
6) high dose ICS + LABA + oral steroid and consider omalizumab

Before stepping up treatment, check puffer technique, adherence, environmental control, comorbidity.

Note that LABAs are never used without inhaled steroids; LABA alone increased mortality in trials

Do not step down unless asthma is well controlled for 3 months.

Parameters of control
daytime sx less than 4x/wk night sx less than 1x/wk normal physical activity mild, infrequent exac, no absenteeism B2 agonist use less than 4x/wk peak flow or FEV1 over 90% of best

Some general differences between asthma and COPD

1) reversible vs fixed obstruction
2) steroid responsiveness higher in asthma than COPD
3) small role for anticholinergics in asthma
4) very rarely use abx for exacerbations in asthma
5) dyspnea, tightness, wheeze in asthma vs dyspnea, cough, sputum in copd
6) early vs. late onset

In the non-responding asthmatic, think about:
1) poor compliance
2) poor inhaler technique
3) environment
4) drugs- B-bl, ASA
5) comorbitites- GERD, sinusitis, allergies, CHF
6) complications- ABPA, churg-strauss, chronic eosinophilic pneumonia
7) psychosocial
8) wrong diagnosis- consider vocal cord dysfcn, airway obstruction, CF (adult)

Links:

Click here for the 2007 NIH asthma guidelines

Acknowledgement:

Some of the above is taken from the University of Toronto Department of Respirology resident handbook

Hyponatremia

Today we discussed a common internal medicine problem, hyponatremia.

Acute vs. chronic cutoff is 48h.

Hyponatremia relative excess of free H2O for a given total body Na or ECFV (whether it's hypo/eu/hyper).

Traditional first breakpoint is by serum osmolality:
1) Hyperosmolal: hyperglycemia (10:3 adjustment), mannitol (IV)
2) Euosmolal: hyperproteinemia, hyperlipidemia (both pseudo; not usually an issue with modern lab techniques), bladder irrigation (dilutional)
3) Hypo-osmolal: Most common

Within Hypo-osmolar, divide by volume status:
Hypo: vomiting, diarrhea, DKA, diuretics, hypercalcemia
Eu: post-op, pain, nausea, pregnancy, SIADH (paraneopl from lung/CNS/pancreas/HL/leukemia or non-neoplastic), beer potomania, psychogenic polydipsia, hypothyroidism, adrenal insufficiency
Hyper: CHF, cirrhosis, nephrotic syndrome, renal failure

A word on SIADH:

Drugs that cause it: The "C's":
cyclosporin, cyclophosphamide, carbamazepine, cisplatin, 1st gen sulfonylureas (like chlorpropramide), antipsychotics (like clozapine), SSRI (OK...not a "C")

SIADH criteria
serum osm less than 275
urine osm more than 100
urine na more than 40
euvolemia
no diuretics
normal thyroid and adrenal function

NB- 'SIADH' with low UNa is not inappropriate b/c hypovolemia should turn on ADH.

Rate of correction:

Be very careful with the hypovolemic, hyponatremic patient (which is very common!). Danger is to volume replete and turn off ADH, causing dilute urine excretion, and rapid increase in Na. Consider ddAVP here; e.g. 2-4mcg IV or SC, even possibly before volume resuscitation. Always monitor urine output and serum lytes closely in this setting.

Aim for an increase of less than 8mEq per 24h (truly dangerous range is 12mEq/24h)
Highest CPM risk: malnourished, elderly, EtOH use (i.e. most people who get hyponatremic!)

Acute or severely symptomatic (e.g. sz, coma, cerebral edema):
3% saline at 1-2ml/kg/h
aim for 2mM/h increase
check Na q2h
d/c when symptoms improve

Othewise, fluid restrict and watch carefully.

Links:

Click here for a NEJM review of SIADH

Click here for the evidence for ddAVP in preventing overcorrection

Dementia

Today we discussed dementia, paricularly with a rapidly progressive course

General classification of dementias:

1) Alzheimer's disease: 60-70%- hallmark is early loss of anterograde memory, with loss of functioning. Late loss of languange function.


2) Non-AD: 30-40%

Vascular- hx of CV risk factors, hx of overt stroke. Imaging shows stroke, leukoencephalopathy, ischemic or degenerative changes. Classically step-wise, with steps overnight.


With Parkinsonism:
- Dementia with Lewy bodies and Parkinson's dementia. Difference is whether parkinsonism was present first for over 1yr, which means PDD. DLB is characterized by nonbizarre delusions, neuroleptic sensitivity, REM sleep behaviour disorder (i.e. no paralysis in sleep, acting out violent dreams), autonomic disturbance
- Progressive Supranuclear Palsy (PSP)- upward, then downward, then lateral gaze palsy. Prominent truncal parkinsonism, with severe postural instability. Very high fall risk. Increased tone. Minimal response to L-dopa.
- Cortico-basal degeneration (CBD)- marked laterality of movement disorder. Apraxia, alien limb possible. Minimal response to L-dopa


Frontotemporal dementia (FTD)
- Frontal: personality change, with executive dysfunction, disinhibition, and/or apathy
- Temporal: Memory loss in 25%, language deficits- all anomic, either fluent or non-fluent with circumlocution and word-finding difficulty.
NB- ALS may present this way


Rapidly progressive dementia- a long, but still incomplete list of potential causes

1) Atypical presentation of primary neurodegenerative dementias (FTD, AD, LBD, PSP, etc.)
2) Structural brain disease (tumors, bleeds, collections, NPH)
3) Medications- Li, serotonin syndrome
4) Seizures
5) Infections (HIV, PML, cryptococcal meningitis, syphillis, malaria, TB, bartonella, Whipple's)
6) Psychiatric illness
7) Prion disorder (CJD, vCJD)
8) Autoimmune (Hashimoto's encephalopathy, others)
9) Inflammation (MS, ADEM)
10) Paraneoplastic (limbic, brainstem, etc)
11) Vasculopathy (vasculitis, intravascular lymphoma, CADASIL)
12) Nutritional (B12, folate, niacin, thiamine)
13) Genetic- late presentation of genetic disorder (e.g. hereditary adrenoleukodystrophy, neuronal ceroid lipofuscinosis, etc.)
14) Toxin (cocaine, EtOH, amphetamines, heavy metals, solvents, chemotherapy)
15) Systemic disease (sarcoid, celiac, CNS lupus, Sjogren's, Behcet's)
16) Metabolic (hypothyroidism, hypercalcemia, etc.)

Investigations:

CBC, lytes, liver, renal, glucose, thyroid, B12. CT scan for subdural, NPH. Possible MRI with gadolinium, EEG.
In correct settings, consider HIV, syphillis, depression, CNS vasculitis (h/a, sz, dementia), prion disease

Links:

Click here for NEJM clinical conference on this topic
Click here for CMAJ review of dementia diagnosis

Idiosyncratic drug reactions

Today we discussed many types of drug reactions. Some important points:

These are immune-mediated, which is distinct from drug toxicity, which everyone will get at high enough level. Idiosyncratic drug reactions (IDRs) are not anaphylactic reactions

IDRs may be single-organ (e.g. hepatitis) or multi-system ("drug hypersensitivity syndrome")

1) Drug hypersensitivity syndrome
Characterized by fever, rash (with or without mucosal involvement), and internal organ involvement (failure). Occurs with incidence of 1 in 1000 to 10000 with these culprit drugs: anticonvulsants (almost all of them), sulfonamides, allopurinol, and dapsone. Timeframe is 2-8 wks after initiation. Sometimes also called "DRESS" or drug reaction with eosinophilia and systemic symptoms)
Most serious:
Stevens-Johnson's, Toxic Epidermal Necrolysis: desquamating skin and mucosal involvement; organ failure. Distinguished by surface area involved. Less than 30% BSA = SJS. More than 50% = TEN; overlap = between. Tx: supportive (inc. burn unit), possible role for steroids, IVIG.

2) Serum sickness-like reaction
Causes fever, arthritis, lymphadenopathy, rash. No internal organ involvement. Timeframe is 7-14d after initiation. Major culprits are cefaclor, minocycline, and bupropion.

3) Drug-induced lupus
Clinically, mainly arthritis, serositis, wt loss. 95% have anti-histone AB, negative anti dsDNA, normal complements.
Major culprits are procainamide, dilantin, INH, hydralazine, methyldopa, quinidine, chlorpromazine, minocycline.
Timeframe may be up to 1-2 years after initiation of therapy

General approach to treatment is to D/C drug, supportive therapy, steroids as dictated by severity.

Some specific drug-rash combinations:
Urticaria: codeine, ASA
Photosensitivity: hydroxychloroquine, chlorpromazine
Psoriasis: lithium, B-blockers
Serum sickness-like reaction: Cefaclor
Fixed drug eruption: Anticonvulsants, sulfonamides

Dilantin kinetics:

Remember that phenytoin exhibits zero-order kinetics after a certain level. This means that only a fixed amount (not proportion) of drug is metabolized after a certain point (which is unknown for a given patient). If this threshold is crossed, a very small increase in dose can cause a big increase in level and toxicity. Increase doses slowly and by small increments (e.g. 25-50mg/d at a time, checking levels).

Links:
Click here for a good overview of idiosyncratic drug reactions
Click here for a NEJM case conference which discusses severe drug reactions
Click here for study of anticonvulsant teratogenicity
Click here for a summary of phenytoin kinetics

Sickle cell anemia

Blood film showing many features of SCD: sickles (blue arrow), Howel-Jolly body (black arrow), targets (red arrow), and nucleated RBC (top left)





Today we discussed sickle cell anemia. Some important points:

Pathophysiology is point mutation on Beta globin gene. Results in Hb polymerization and rigid, elongated RBC.

Sickling is promoted by hypoxia, low temp, low pH, volume depletion.

Notes on diagnosis:
1) Hemoglobin electrophoresis- shows 40% HbS in carriers (~60-40 split), and 90%+ HbS in homozygotes.
2) "Sickledex" screening test does not distinguish carriers vs. homozygotes vs hemoglobin SC. Looks for presence of sickling on hypoxic conditions.
3) Blood film will often show no sickles in carriers, but there should always be some sickles in SS. If you see predominantly targets, ddx includes hyposplenism and SC disease (shows almost all targets)

Heterozygotes are usually asymptomatic, with occasional sickles on PBF, but normal Hb levels.

Homozygotes have moderate to severe hemolytic anemia, and have crises and complications

Crises and complications:

Vaso-occlusive crisis: in bone, muscle (very painful). Also at increased risk for stroke even in children (on ddx of stroke in young). May develop 'Moya Moya' (hypervascularity from chronic hypoxia- increased hemorrhage risk)
Resp- chest crisis- defined by infiltrates and hypoxemia (not due to CHF).
Renal- hematuria, tubular defects (acidic, hypoxic environment causes sickling).
Marrow- aplastic crisis- Keep close eye on Hgb in patients with low retics (can drop rapidly) Pts may get parvo and have severe aplastic crisis (can't keep up with increased baseline demand).
ID- hyposplenic- susceptible to encapsulated microorganisms. Risk of osteomyelitis (esp with Salmonella)
Others: priapism, retinopathy/retinal occlusion, leg ulcers

Crisis management:
1) O2 whether hypoxemic or not
2) Fluids
3) Correct precipitating factor (infection, volume depletion, etc)
4) Analgesia
5) Consider transfusion strategy

Transfusions in SCD:
In general be sparing with transfusions because these patients develop antibodies and it's difficult to find units when really needed. Fe overload is also a problem with frequent "sub-necessary" transfusions. Simple pain crisis does not require a transfusion.

Conventional transfusion guidelines:
-aplastic crisis (i.e. below baseline hgb with low or inappropriately normal retics)
-Hb below 50 (may accept lower than usual because baseline may be low)
-active bleeding, etc
STOP TRANSFUSING WHEN hematocrit >0.35 (hyperviscosity and stroke risk)

When to exchange transfuse (i.e. ~14 units exchange)

1) Chest crisis (FiO2 over 40%, infiltrate, no pulmonary edema)
2) Stroke (ischemic or hemorrhagic)
3) Pre-operatively for major surgery to HGB S below 30%
4) Severe sepsis, multiorgan failure
5) Retinal occlusion
6) Fetal distress
7) Priapism (relative indication)

Hydroxyurea in sickle cell disease

Adults with 3 or more painful crises/year; increases proportion of HbF
reduces frequency of painful crises and chest crises. Also mortality benefit (secondary outcome).
Need to monitor hepatic fcn and counts carefully.


References:

Click here for BMJ review of sickle cell disease management

Click here for NEJM review of hydroxyurea in SS disease

Colitis

Today we discussed the approach to bloody diarrhea. Some things that came up:

Bloody diarrhea implies colitis (of some etiology)
Triad of fever, bloody diarrhea, lower abdo pain defines "dyssentry".

Differential diagnosis:
Infectious colitis: campylobacter, yersinia, samonella, shigella, E. Coli (enterohemorrhagic), C.diff. In immunocompromise: CMV.
Ischemic colitis: seen in patients with severe vascular disease, hypercoagulable states, A-fib
Inflammatory colitis: UC (bloody diarrhea and mucous are hallmark symptoms), Crohn's
Post-radiation colitis

Important history:
travel, food, others with same symptoms, medications, hospitalization, sexual contact, symptoms suggesting IBD (inc. extra-intestinal), fhx, constitutional symptoms, immunosuppression risk factors


Antibiotics in infectious diarrhea:

Most causes do not require (and sometimes are worsened by) antibiotics.

Exceptions where Abx are indicated:
C. Difficile
Shigella (to prevent transmission)
Enterotoxogenic E. coli (ETEC) = "traveller's diarrhea", not 0157 (that is enterohemorrhagic)
Entamoeba histolytica
Giardia
Only in severe cases of yersinia, campylobacter, salmonella

Abx are harmful in
Enterohemorrhagic E. coli (as in Walkerton)

Abx not usually needed for
salmonella, campylobacter (most common causes of infectious colitis). Note that campylobacter is not covered by ciprofloxacin (if need to treat, use macrolide)


Extraintestinal manifestations of IBD

Eyes- uveitis
Skin- eryhtema nodosum, pyoderma gangrenosum
GI- PSC (esp UC), stones
Renal (stones- IBD affects oxalate metabolism by unabsorbed bile salts binding calcium, allowing increased oxalate absorption)
Arthritis- Seronegative, large joint symmetric. Either peripheral, which parallels IBD activity, or axial, which is usually independent of IBD activity


Toxic megacolon

Non-obstructing dilation of the colon.
May occur from infectious etiology as well as IBD.
Clinical: tachycardia, hypotension, fever, volume depletion, altered sensorium.
AXR: greater than 6cm at transverse, thumbprinting (big haustra), pneumatosis coli.


Reference:

Click here for a NEJM review of infectious diarrhea

Syncope

Today we discussed an approach to syncope. Some important points:

Definition:
Abrupt loss of consciousness followed by rapid, complete recovery

Is it syncope?


All of dizziness, presyncope, drop attacks, and vertigo do not involve loss of consciousness.

Sz vs. syncope: features before, during, and after event:

1) Pre- aura in sz vs. pain, exercise, micturition, defecation, stress usually syncope
2) During- rhythmic movements, >5 min event suggest sz; sweating, nausea suggest syncope
3) Post- disorientation to event, slow to return to consciousness, Todd's paralysis suggest sz. Completely normal post-event suggests syncope.

Differential

1) Cardiac-
Arrhythmic: brady (blocks), tachy (VT, SVT).
Non-arrhythmic: HOCM, AoS. Less common: myxoma, pulm HTN, tamponade, massive MI, MS, Aortic dissection

2) Non-cardiac-
Neurocardiogenic (i.e. 'vasovagal'), neurological (carotid sinus hypersensitivity, subclavian steal, bilat carotid stenosis, posterior TIAs, migraine) orthostatic, psychogenic.
Metabolic: (hypoglycemia, hypoxia, hyperventilation)
"situational" (micturition, defecation)
menstrual

Prognosis

The presence of heart disease is the most important prognostic factor
Cardiac cause- 1 year mortality 18-33%
Non-cardiac cause 0-12%
Unknown cause 6%
NB- the high mortality from cardiac cause is driven by underlying cardiovascular disease, not arrhythmia per se. Data from 1980's.

Evaluation:

Initial: history, physical, orthostatic BP, ECG. If no confirmed or suspected cause, these pts fall under "unexplained" category. If suspected cause, confirm with appropriate testing.

Unexplained: Consider 2D echo, stress testing. If normal, neurally mediated syncope is likely. Consider tilt table testing for neurocardiogenic syncope if recurrent episodes.

Structural heart disease, abnormal ECG: Holter, EP study, loop recorder

Outpatient vs. inpatient management:
Admit when rapid evaluation is necessary because of concern about serious arrhythmia, sudden death, newly diagnosed serious cardiac disease. Pts with facial trauma, bleeding, PE, severe orthostatic hypotension should be admitted.

Reference:

Click here for good review of syncope from Circulation

Ascites

At physical exam rounds we discussed ascites and liver disease

Some key points:

Most sensitive findings (i.e. make it unlikely if not present):
1) flank dullness
2) bulging flanks
3) shifting dullness
4) peripheral edema
-history of increased girth, weight gain, ankle swelling

Most specific findings (i.e. make it likely if present)
1) fluid wave
2) shifting dullness

An approach to the examination in liver disease (besides examining the liver itself)

1) Signs of decompensated liver disease
-jaundice, scleral icterus, dark urine (high bilirubin)
-petechiae, ecchymoses (coagulopathy)
-edema (hypoalbuminemia)
-asterixis, level of consciousness (encephalopathy)

2) Signs of chronic liver disease / hyperestrogenemia signs
-nail and hand findings
-muscle wasting
-spider nevi
-gynecomastia
-testicular atrophy

3) Signs of portal hypertension
-ascites
-splenomegaly
-dilated abdominal veins (extreme of this is caput medusae)
-hemorrhoids

4) Signs suggesting the etiology of liver disease
-cardiac exam (liver + heart involved in "cardiac cirrhoisis", EtOH, hemochromatosis, amyloid, sarcoid)
-resp exam (liver + lungs involved in sarcoid, alpha-1 antitrypsin deficiency)
-CNS (liver + movement disorder in Wilson's)
Many more...

Reference:

Click here for JAMA rational clinical exam on ascites

Hypercalcemia

Today we discussed hypercalcemia. Some issues that came up:


Vomiting

One of many possible approaches:

Intraperitoneal causes

Obstruction: pylorus (gastric outlet obstruction), SBO, LBO
Infection: viral gastroenteritis, bacterial
Inflammation: cholecystitis, pancreatitis, appendicitis, hepatitis
Motor: gastroparesis, GERD, esophageal spasm

Extraperitoneal causes

Cardiovascular: MI, CHF
CNS: cerebellar, brainstem, raised ICP (masses, bleed, hydrocephalus), migraine
Inner ear: labyrinthitis
Medications: post-op, chemotherapy, antibiotics, OCP, oral hypoglycemics
Metabolic: uremia, hepatic failure, calcium, sodium, DKA, adrenal insufficiency
Pregnancy

Clues:
Bilious suggests from distal to duodenum
Undigested food suggests gastric outlet obstruction, gastroparesis or Zenker's diverticulum
Feculent suggests colonic obstruction
Immediately after eating suggests gastritis, gastric outlet obstruction


Hypercalcemia

Symptoms: GI- anorexia, n/v, abdo pain, constipation. Renal: stones, polyuria. Neuro: weakness. Cardiac: arrhythmias

Etiology:
Useful first division is by PTH level

1) High PTH- expect high Ca, low PO4.
A) primary/secondary/teriary hyperparathydoidism, parathyroid hyperplasia
B) lithium
C) familial hypercalcemic hypocalciuria

2) Low PTH
PTHrP from malignancy (esp. SCC- lung, H+N)
hypervitaminosis D- expect high Ca and high PO4- from granulomatous disease, lymphoma)
OAF = IL6 (local paracrine effect; in breast and hematological cancers)
Direct effect of mets (e.g. prostate, lung, etc.)
Myeloma
Medications- HCTZ, Ca, vit. D
Milk alkali syndrome
Hyperthyroidism

As inpatient, #1 cause = malignancy
As outpatient, #1 cause = primary hyperpara


Tx: Fluids!. Consider bisphosphonate if malignancy-related or v. high (but takes days to work)
Calcitonin by nasal spray or subq. If hyper D from sarcoid or lymphoma, possible steroids. Avoid lasix since most patients are profoundly volume depleted. Last resort is dialysis


Milk-Alkali syndrome

Triad of hypercalcemia, met alk, renal failure assoc with ingestion of large amts calcium, alkali

Once common because of PUD treatement. Making resurgence b/c of calcium for osteoporosis, and prevention of secondary hyperparathyroidism in CKD

Sequence: hypercalcemia, dec GFR, met alkalosis ("contraction"). Hypercalcemia per se stimulates renal bicarb fomation.

Pts on vit D, thiazides, vol contraction, CKD are at higher risk


Some links:

Click here for NEJM clinical problem solving case on hypercalcemia

Click here for a review of calcium disorders in renal disease

Bronchiectasis

Defined as inflamed, easily collpsible airways, with obstruction on PFTs. Dx by chronic sputum, bronchial wall thickening, and luminal distension on CT.

Clinical features are cough, sputum for months to years. Dyspnea, wheeze, pleuritic c/p, hemoptysis also seen.

Pathophysiology is acquired disorder of bronchi and bronchioles; abnormal dilation of walls and scarring.

Causes:

Focal: Foreign body, TB, old infection (usually a serious pneumonia)

Global: cystic fibrosis, dysmotile cilia (Kartagener's), allergic bronchopulmonary aspergillosis, nontuberculous mycobacterial infection, alpha-1 anitrypsin deficiency, RA, IBD

NB- "Traction bronchiectasis" is common in pulmonary fibrosis.


Investigations:

1) CXR, high-resolution CT
2) PFTs when stable
3) ECG (for cor pulmonale)
4) CBC, immunoglobulins, Ig subclasses (esp for IgE- ABPA), RF, alpha-1 antitrypsin, HIV
5) Sputum for bacteria, AFB (NB- nontuberculous mycobacteria), fungi
6) Sweat Cl +/- genetic testing
7) TB skin test
8) Aspergillus precipitins (for allergic bronchopulmonary aspergillosis)
9) Ciliary studies (e.g. EM)

CXR- tram lines

CT- dilated airways (more than 1.5x accompanying vessel), thickened bronchial walls, cysts, 'signet ring sign'


Exacerbations

Heralded by increased sputum, SOB, pleuritic pain, hemoptysis. Rarely do you see a new infiltrate.

Organisms: H. Flu, pseudomonas, st. pneumo. Fluoroquinolone is reasonable 1st line.

Prevention: several variations on chronic Abx, possibly inhaled tobramycin.

Chest physio is vital; hydration, mucolytics, bronchodilators all have role.


Reference:

Click here for a review from Chest on bronchiectasis

Hemoptysis

"Vincenzo Grimaldi has tuberculosis. His physician and several female relatives tend to him in his home while a family member prays to the Martyred Saints Alfio, Cirino,and Filadelfo for his swift recovery" - from US National Library of Medicine website

Today we discussed hemoptysis. Some issues that came up:

"Massive" is defined as >600cc in 24h (100-600cc depending on source). In these cases, souce of bleeding in most cases is bronchial artery (not pumonary)

Differential

For non-massive, bronchitis, bronchogenic carcinoma, and bronchiectasis are most common in North America. Frequency of different causes depends on the population (i.e. high prevalence area for TB, etc.)

1) Infection
Bacterial- community or hospital-acquired pneumonia with blood-tinged sputum (as opposed to massive), lung abscess, necrotizing pneumonia (St. aureus, klebsiella, anaerobes)
Mycobacterial- TB
Fungal- aspergillosis, coccidiomycosis

2) Neoplastic
Primary- Endobronchial tumor (carcinoma, adenoma), carcinoid
Secondary - Note that hemoptysis in metastatic ca is rare

3) Bronchiectasis

4) Pulmonary vascular
PE, Pulmonary HTN, AVM (as in HHT)

5) Vasculitis
Goodpasture's, Wegener's, Microscopic polyangiitis

6) Cardiac
Mitral stenosis, severe LV failure

7) Others:
trauma, post-procedural, drugs

Management of massive hemoptysis:

-Hemodynamic support, reverse coagulopathy
-R/O epistaxis or UGIB
-Position with bleeding side down
-Call anesthesia, respirology, thoracic surgery
-Determine which side is source; anesthesia can do bronchial isolation
-Rigid bronchoscopy with suction catheter, lavage with cold epi-saline
-Bronchial artery embolization by interventional radiology

Links:
Click here for a good review of massive hemoptysis management from Thorax
Click here for NEJM clinical-pathological conference on hemoptysis

Renal failure in lupus

Glomerulus with thrombi in a case of thrombotic microangiopathy related to SLE


Today we discussed renal failure (or acute kidney injury) in the setting of lupus. This scenario raises many diagnostic possibilities. Some important points:

Whenever faced with a new (or worsened) problem in the setting of a pre-existing disease, a useful dichotomy is whether this new problem is related or unrelated to the underlying disease.

Directly related to SLE
1) Lupus nephritis
2) Renovascular disease
3) Thrombotic microangiopathy (TTP-like situation), especially in context of antiphospholipid antibodies
4) Libman-Sachs endocarditis embolizing to kidneys (very rare)

Indirectly related to SLE
1) Prerenal state from cardiovascular event / disease (note high risk of CV disease in SLE)
2) Tubulointerstitial disease from medications
3) Prerenal state from medications (e.g. NSAIDs)

Unrelated: Usual approach of prerenal, renal, postrenal.

As in any case of acute kidney injury, the evaluation must include

1) Clinical indications for dialysis (pulmonary edema, uremic pericarditis)
2) Clues to the etiology (BP, volume status, rashes, arthritis, etc)
3) Urinalysis (the "physical examination of the kidney")
4) Assessment of serum and urine electrolytes, osmolality, lab evaluation for secondary causes

Lupus Nephritis

Accumulation of immune complex deposits is the pathologic mechanism, esp. in glomeruli.

Abundance and intraglomerular distribution of IC's are correlated with severity of lupus
nephritis. This is the basis of the WHO classification:

I- no glomerular abnormalities or minimal mesangial.
II- mesangial lupus nephritis- mesangial immune deposits. Variable hypercellularity
III- focal, segmental lupus nephritis; scattered peripheral glomerular deposits, with focal necrotizing and proliferative changes in fewer than 50% of glomeruli
IV- diffuse proliferative GN; extensive subendothelial deposits and necrotizing changes
V- membranous- subendothelial deposits with few or no mesangial deposits. This is not a GN cause (i.e. not as 'nephritic'; more 'nephrotic')

Notes: there is overlap between classifications, and this does not represent a progression. There is a high proportion of pts who evolve from one form to another.

Thrombotic microangiopathy / TTP in SLE

It is well established that autoimmune disease is a risk factor for TTP; checking for hemolytic anemia and RBC fragments (schistocytes) is important to exclude this condition which has a 90% mortality untreated (i.e. without plasma exchange)

Links:
Click here for NEJM clinical-pathological conference on renal failure in SLE
Click here for a presentation I gave on the link between TTP and autoimmune disease (esp. SLE)

Tuberculosis

Today we discussed issues related to tuberculosis

Risk factors for initial infection:

1) Native of country with high prevalence

2) Homelessness

3) History of incarceration

4) Aboriginal origin

5) Household exposure to case of active TB

6) Healthcare worker

Risk factors for reactivation:

1) HIV

2) TNF antagonist therapy

3) Head and neck malignancy

4) DM2

5) ESRD

6) Silicosis

7) Chemotherapy

8) Prednisone > 15mg x > 2 weeks

Some of the many possible presentations:

Pulmonary: constitutional symptoms, chronic cough, hemoptysis, apical, posterior upper, or superior lower lobe opacity

Miliary- widespread dissemination to lungs, spleen, liver, marrow, nodes, adrenals

Lymphadenitis- "scrofula" when neck nodes burst

Adrenal insufficiency (#1 cause worldwide)

Osteomyelitis (Pott's disease)

Genitourinary

Pericardial effusion

Large joint arthritis

Meningitis

Abdominal- terminal ileal disease, malabsorption, peritonitis

Therapy: Direct observed therapy (DOT) is optimal

4 drugs for 2 months, 2 drugs for 4 months

Initially INH, rifampin, pyrazinamide, ethambutol. Narrow by sensitivity result

A few TB eponyms

Gohn's complex- primary pulmonary lesion and associated adenopathy on CXR
Gibbus deformity- vertebral collapse from Pott's disease
Rasmussen's aneurysm- pulmonary artery aneurysm from TB

Some references

Click here for NEJM review on latent TB infection
For the connaisseur, click here for IDSA treatment guidelines
Click here for CMAJ review of extrapulmonary TB

Fever in the returned traveller

Today we discussed issues related to fever in the returned traveller

Some points that came up:

The red herring effect:
Do not be completely distracted by the travel history and its accompanying exotic possibilities; remember to look for and exclude the common causes of fever (i.e. common bacterial and viral infections, etc).

Important points on history:
-detailed travel itinerary (for location, activities) and dates (for incubation periods)
-whether pre-travel advice and appropriate prophylaxis was obtained
-specific exposures: sexual history, fresh water, animals, mosquitos

The VFR effect
Travellers "visiting friends and relatives" (i.e. VFR) are a particularly high risk group for serious travel-related illness; they are less likey to seek pre-travel counselling and take indicated prophylaxis. In contrast, they are more likely to have high-risk exposures and waning immunity due to prolonged absence.

Selected features of specific diagnoses (not intended to be exhaustive!)

Malaria- any fever in returned traveller from tropics is malaria until proven otherwise. Diagnosis by thick (sensitive) and thin (specific) smears; send multiple. Falciparum is the most virulent type

5 Malaria Questions:
1) Where it was acquired, and the resistance patterns there
2) What type is it? (much more worried if falciparum)
3) What is the degree of parasitemia (% of RBCs carrying); > 5% can be fatal
4) Was the pt on prophylaxis, taking it properly?
5) Is this "severe malaria"; coma, severe prostration, anemia, ARF, severe jaundice, resp failure, hypoglycemia, shock

Dengue- Wide spectrum of clinical manifestations. Retrobulbar h/a, muscle and joint pain "break bone fever"; rash in 50%. Leukopenia and thrombocytopenia common. Dengue Hemorrhagic Fever is feared complication; more common in previously exposed.

Typhoid- Abdo pain, fever, chills. Evanescent "rose spots" on abdomen or trunk. Relative bradycardia for fever is classic. Diarrhea or constipation. May have leukopenia or leukocyosis, anemia, transaminitis. Diagnosis by blood or stool cultures. Bone marrow Bx is 98% sensitive.

Others: schistosomiasis, leptospirosis, rickettsial diseases, hepatitis A, hepatitis B, HIV seroconversion reaction...

Some useful links

Click here for VFR paper from JAMA
Click here for GeoSentinel survey for conditions by geographical location
Click here for Gideon website- input location, symptoms, duration and receive weighted probabilty of different diagnoses
Click here for CDC website

Aortic Stenosis

At physical exam rounds, we discussed aortic stenosis.

Some key points:

Possible findings:

Vitals- Narrow pulse pressure

Pulses- Carotid may have low volume (parvus) and slow rate of rise (tardus). Brachio-radial delay, apical-carotid delay

JVP- Elevated if R heart failure as consequence of pulmonary edema (late)

Precordial palpation- Displaced, sustained apex, palpable S4, thrill

Heart sounds- Diminished S2, paradoxically split S2, S4

Murmur- Mid to late- peaking crescendo-decrescendo systolic murmur loudest in aortic area radiating to R clavicle, R carotid, or apex (Gallavardin)


Findings shown to rule out or rule in AoS

Sensitive (used to rule out)

Any systolic murmur

Murmur radiation to R clavicle (JGIM) or R carotid (JAMA) - see references


Specific (used to rule in)

Pulsus parvus et tardus (JAMA and JGIM)

Decreased intensity of S2 (JAMA and JGIM)

Mid to late-peaking systolic murmur (JAMA and JGIM)

Brachio-radial delay (JAMA)

Apical-carotid delay (JAMA)












Flow diagram from Etchells et al


References:

Click here for JGIM bedside clinical prediction rule

Click here for JAMA article on abnormal systolic murmur

Alcohol-related Liver Disease

Art Deco glamorization of excessive martinis







Today we discussed issues related to alcoholic liver disease and SBP. Some points that came up:

Risk factors for SBP
1) Prior SBP
2) GI bleed
3) Child's C cirrhosis
4) Ascitic fluid protein 10g/L

When to suspect SBP (and therefore perform diagnostic tap)
1) Admission of all cirrhotic pts with ascites, regardless of reason for admission
2) Patients with ascites and with GI bleed routinely before abx (20% have SBP initially, 40% by discharge)
3) Patients with ascites and any of abdominal pain, rebound, vomiting, diarrhea, fever, leukocytosis, encephalopathy (although NB- abdo pain is often absent)

SBP diagnosis
Ascites PMN > 250 or WBC > 500. If WBC > 1000 or polymicrobial culture or protein > 10g/L, suspect secondary peritonitis (i.e. intra-abdominal persistent source- abscess, perforation, etc).

Evidence-based prophylaxis in cirrhosis
1) Primary SBP prophylaxis in cirrhotic patients presenting with GI bleed: quinolone or ceftriaxone
2) Secondary prophylaxis of SBP: daily norfloxacin or weekly ciprofloxacin
3) Screening OGD at time of diagnosis, repeated q1-3 years depending on compensation
4) Non-selective B-bl (i.e. nadolol) for patients with varices (including those which have not bled) 5) Endovascular ligation (i.e. banding) for high-risk varices
6) Combination of B-bl and nitrates may slow progression of portal HTN
7) HCC screening by u/s q6-12 months for cirrhotic patients and high-risk HBV carriers
8) Hepatitis A and B vaccination for all patients with chronic liver disease

Alcohol withdrawal seizures
1) Generalized
2) Possibly recurrent (i.e. "rum fits")
3) Minimal post-ictal phase
4) Not followed by Todd's (suggests focality- suspect SDH, other focal abnormality)
5) Usually self-resolving

Wernicke-Korsakoff's syndrome
1) Ataxia - "magnetic gait"
2) Ophthalmoplegia- commonly bilat 6th CN. Possibly also 3rd CN
3) Amnesia- anterograde and possible mild retrograde (cannot learn new material; often confabulate)
1+2 = Wernicke's, 3=Korsakoff's


Some references
Click here for cirrhosis guidelines
Click here for esophageal varices / portal HTN guidelines
Click here for RCT on withdrawal sz treatment
Click here for evidence for empiric abx in cirrhotics with GIB

Meningitis

Gram positive diplococci in CSF which grew strep. pneumo

Today we discussed meningitis, a serious infection that requires prompt initiation of life or neurological function-saving therapy before confirming the diagnosis. Although the discussant was, well, substandard, some important points still came across

(for those not there, the discussant was me, so no emails necessary)

Some issues that came up:

Common sources of infection in nursing home patients:
1) Urinary tract
2) Pneumonia (would be 'healthcare associated'- different abx coverage)
3) Skin

Reasons for a patient not to improve despite appropriate abx for an infection:
1) Not receiving therapy (non-adherence, vomiting, etc)
2) Resistant organism
3) Wrong diagnosis
4) Source not being penetrated (e.g. underdosed, abscess)
5) Persistent source not dealt with (e.g. osteomyelitis, sacral ulcer)

Common organisms in meningitis:
1) St. pneumo
2) N. meningitidis
3) H. flu
4) Listeria

Order depends on patient; listeria more common in older, immunocompromised. Think of unusual causes in right setting (e.g. cryptococcus, TB). Even though cryptococcal meningitis (which may present subacutely) comes to mind in HIV, invasive st. pneumo infections are far more common in HIV than in the general population.

Important risk factors to ask about:
Travel, contacts, HIV RFs, sinus or ear infections, injection drugs, head trauma.
The lack of all of fever, altered mental status, or neck stiffness virtually rules out meningitis

Some physical exam points:
1) Kernig's and Brudzinski's signs were described a century ago in patients with end-stage TB meningitis. They have low sensitivity, but high specificity.
2) Jolt accentuation (i.e. patient turns own head horizontally at 2-3 /second) is 100% sensitive, but very non-specific. Therefore, lack of it essentially rules out the diagnosis (although the JAMA article excluded immunocompromised patients, so be careful)

Empiric treatment (i.e. before CT scan, before LP. Ideally after blood cultures)
1) ceftriaxone 2g (for NM)
2) vancomycin 1g (for SP- there is pen-resistant SP in the community)
3) ampicillin 2g (if suspect listeria)
4) dexamethasone 10mg (with antibiotics)- see references
5) +/- acyclovir if suspect HSV encephalitis (rash, sz, focal deficits)- need to hydrate aggressively
Tailor Abx once culture result back +/- HSV PCR is back


LP is mandatory! Even though Abx are started, you need a diagnosis.


Causes of very low CSF glucose
1) Bacterial meningitis
2) TB
3) Fungal
4) HSV encephalitis

Some references:

http://jama.ama-assn.org/cgi/content/full/282/2/175

http://content.nejm.org/cgi/content/abstract/347/20/1549

http://jama.ama-assn.org/cgi/content/full/296/16/2012

Vasculitis

p-ANCA immunofluorescence

Today we discussed the diagnosis and management of vasculitis, specifically ANCA-associated vasculitis. These diseases are rare, complex, multisystemic, and present many challenges to everyone involved (including those trying to blog about it). Good thing we had an expert!


When to suspect vasculitis?

1) Multiorgan involvement otherwise unexplained

2) Systemic symptoms (constitutional, etc. ) otherwise unexplained

3) Organ ischemia or infarction (bowel, renal, myocardial, etc)

4) Common condition in uncommon age group (MI, pulmonary edema, etc.)


How to classify vasculitis:

May classify by vessel size, by complement levels, by ANCA associated or not, and other features. Most commonly vessel size (Chapel Hill classification)

Large: Takayasu's, GCA

Medium: Kawasaki's, isolated CNS

Medium +/- small: PAN, Churg-Strauss, Wegener's

Small: HSP, cryoglobulinemia, hypersensitivity, microscopic polyangiitis


Basic features of some vasculitides (not intended to be exhaustive!)

Takayasu's:
pulse deficits, fever, malaise; may cause aortitis or dissection

Giant cell:
>50, sudden onset of pain, stiffness, fever, temporal h/a. Often pulse deficits, aortitis, aortic insufficiency

Kawasaki's
children with acute onset rash, fever, conjunctivitis. Often associated with coronary arteritis

Wegener's
fatigue, malaise, fever, inflammation of sinuses, kidneys, lungs. Also often cutaneous vasculitis. Often cANCA +ve

Microscopic polyangiitis
leukocytoclastic vasculitis, glomerulonephritis, hemoptysis, abdo pain. Often p-ANCA +ve

Churg-Strauss
Asthma, eosinophilia. Renal involvement is rare. p-ANCA often +ve

PAN
Assoc with HBV or HCV antigenemia. Fatigue, HTN, fever, renal failure, rash, mononeuritis multiplex. Marked HTN is classic for acute onset. May present as testicular pain.


Non-vasculitic causes of ANCA positivity

IBD, autoimmune hepatitis, CF, TB, many drugs (esp. PTU, methimazole, hydralazine, minocycline).

Some references for vasculitis diagnosis and management

http://www.bmj.com/cgi/content/full/338/apr22_2/b1461

http://jama.ama-assn.org/cgi/content/full/298/6/655

http://content.nejm.org/cgi/content/short/348/4/333

Welcome!

Welcome to Tangents, the Toronto Western Hospital morning report blog.

This was the idea of Isaac Bogoch, one of last year's CMRs, and I'd like to continue his great work this year.

The goal is to briefly summarize the topics discussed and give you links to some more detailed resources if you're interested.

Please feel free to give me any feedback on how to make it more useful to you.

David

UGIB

On Tuesday, we discussed issues related to upper GI bleeds.

Gastric ulcer with ASA tab in it!

Issues that came up:

DDx
-Ulcer (NSAIDS, H pylori) DU in 2nd/3rd part of duodenum suggests Zollinger-Ellison. Gastric ulcer: think of gastric cancer
-Varices (EtOH, hepatitis). High pressure venous system = big bleed
-Mallory-Weiss tears: vomiting hx. This is partial, vs. Boerhaave: rupture
-Esophagitis/gastritis (reflux, NSAID)
-Portal HTN gastropathy (like varices in stomach)
-Others: Dieulafoy's lesion, epistaxis, many others.

Checklist approach to acute UGIB management
1) Large bore IV access- at least 2
2) Group and screen, be ready to transfuse
3) Reverse any coagulopathy
4) PPI- IV or PO
5) Octreotide if known varices or high probability of variceal etiology
6) GI consult, possible urgent endoscopy

H. Pylori:
Acquisition: usually from childhood due to contaminated drinking water. Spread can occur person to person, especially within households.
Diagnostic tests:
Serology: Sensitive, but does not differentiate active vs. past infection
Urea breath test: Differentiates active vs. previous infection
Biopsy: Gold standard

Ferritin in Fe deficiency:
From Guyatt et al:
Likelihood ratios of Fe def (compared to gold standard of bone marrow bx):
Ferritin: LR
>100: 0.13
45-100: 0.46
18-45: 3.12
<18: 41.47
Cutoff of 41 is 98% Sn and 98% Sp

Some useful references- may need U of T computer to access full text.

Diagnosis of Fe deficiency:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2178409&dopt=Abstract http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1993290&dopt=Abstract

UGIB management:

http://content.nejm.org/cgi/content/full/359/9/928

http://www.cmaj.ca/cgi/content/full/174/10/1433