Fever in a Returning Traveler

Approach to fever in the returning traveler:

1) History:

• Detailed travel hx with dates (to calculate incubation period)
• Exposure history (mosquito bites, water, food)
• Visiting friends and relatives vs staying in tourist areas
• associated signs and symptoms
• Duration and pattern of fever
• immunizations tatus
• Use and adherence to antimalarial chemoprophylaxis

2) Differential Diagnosis (not an exhaustive list!)

• Must rule out MALARIA
• Incubation period: anywhere from 2 wks to a year.
• Plasmodium falciparum: must be immediately ruled out as can be rapidly fatal
• Non-falciparum (P. vivax, P. ovale, P. malariae, P. knowlesi) cause febrile illness but are rarely fatal
• Must keep malaria on the differential, even if on chemoprophylaxis due to resistance
• "hectic" fever +/- headache, cough, GI problems.
• Invx: thick and thin smears x 3, rapid antigen testing, CBC (thrombocytopenia without leukocytosis is characteristic, may have anemia from hemolysis), bili, liver enzymes
• Complications: altered LOC, seizures, acidosis, ARDS, liver failure, severe hemolysis, renal failure, cerebral malaria
• Must start antimalarials parenterally if severe infection or if levels exceed 4% of visible erthrocytes
• Dengue
•  Caused by a mosquito-borne flavivirus in tropical and subtropical areas
• Incubation period of 4-7 days
• Clinical Sx: lymphadenopathy, erythema/nonspecific maculpapular rash, leukopenia and thrombocytopenia
• Serious infection: dengue shock and dengue hemorrhagic fever
• Clinical diagnosis + confirmed with serum antibody titers
• Rickettsia
• Triad of fever + headache + myalgia
• Examples: African tick typhus, Mediterranean tick typhus, scrub typhus
• Transmitted by arthropods (painless eschar at inoculation site) in grassy areas
• Leptospirosis
• History of exposure to fresh water
• fever+ myalgia + headache + rash (Conjunctival suffusion is a diagnostic sign)
• Typhoid
•  Causal agent: Salmonella enterica. Fecal oral transmission
• Sx of fever+abdo distension + constipation+lymphadenopathy
• Invx: Leukopenia +thrombocytopneia. Dx by blood C+S.
• Treated with fluoroquinolone/3rd gen cephalosporin

See the following article for further details: Illness after international Travel 

Thyrotoxicosis

Today we talked about an interesting patient with thyrotoxicosis, here are some things we discussed

1) Thyrotoxicosis vs Hyperthyroidism

• Thyrotoxicosis implies symptomatic excess thyroid hormone, without referring to an etiology
• Hyperthyroidism implies excess intra-thyroidal production of hormone
• Causes for thyrotoxicosis can be divided into 1) Disorders associated with normal or high radioiodine uptake or 2) Disorders associated with low or absence radioiodine uptake

2) Normal or High radioiodine uptake

• Graves disease
• Toxic multinodular goiter
• Toxic adenoma
• Iodine induced hyperthyroidism: i.e. CT contrast or amiodarone (iodine uptake may be low in this case if exogenous iodine has a long half-life or continues to be given, as it will dilute the radioactive tracer)
• Trophoblastic disease/germ cell tumours: mediated by beta-HCG which cross reacts with TSH receptors. Examples include: hydatidiform moles/choriocarcinoma in females and testicular germ cell tumours.
• Secondary hyperthyroidism from a functioning pituitary adenoma

3) Low or absent radioiodine uptake

•  Thyroiditis:
• Pyogenic thyroiditis
• Viral thyroiditis
• Hashimoto's thyroiditis
• Postpartum thyroiditis (a form of Hashimoto's occuring postpartum)
• Radiation thyroiditis
• Palpation thyroiditis (after a surgical excision on the thyroid from it vascular bed)
• Drug induced: amiodarone, lithium

Liver abscess

Types of Liver abscess:
1) Bacterial aka pyogenic
2) Parasitic (amoebic)
3) Fungal

Pathogenesis:
1) Ascension of bacteria from biliary tree (40-50% of cases)
2) Portal vein spread (from intra-abdo source i.e. diverticulitis, appendicitis)
3) Hematogenous spread
4) Direct inoculation from trauma or surgical procedure
5) Cryptogenic

Risk factors
1) Diabetes
2) Hepatobiliary/pancreatic disease
3) Malignancy
4) Liver transplant
5) Immunocompromised: HIV/AIDS

Bugs commonly involved: mostly polymicrobia aerobes + anearobes
1) Gram positives: Staph, microaerophilic Strep, Strep milleri (abscessogenic), enterococcus
2) Gram negatives: Klebsiella, enterbacteriacea coli
3) Anaerobic: fusobacterium, bacteroides (may not be grown on culture)
4)  Fungus
5) Hydatiform cyst echinococcus: from dogs
6) Amoebic liver abscess: entamoeba histiolytica (fecal oral route)

Treatment of pyogenic liver abscess:
1) Abx to cover gram+/-/anaerobes (a penicillin, aminoglycoside/cephalosporin and metronidazole)
4) Source control: perc drainage

See the following article for more about liver abscesses Liver abscesses and Hydatid disease

Empyema

This is my catch-up blog about empyema, which we discussed on Tuesday!

1) Thoracic empyema

• Defined as pus in the pleural fluid (high PMN count) and or pH  less than 7.20. Also has high LDH due to lysis of PMNs. Progression to an empyema occurs over time and patients present subacutely with a long hx of SOB, cough etc. A dense layer of fibrin can deposit on the visceral and parietal pleurae, leading loculation and worse prognosis. This anaerobic environment leads to the proliferation of anaerobes and other bacteria.
• Common symptoms include pleuritic chest pain, dyspnea and sputum production. Those with aspiration risk, underlying lung disease, diabetics and immunocompromised are at higher risk.
• Physical exam reveals dullness to percussion, decreased breath sounds, decreased fremitus and a loss of egophony.
• Common bacteriology:
• Prevalent bacteria include: Streptococcus milleri, Staphylococcus aureus, enterobacteriaceae, strep pneumonia, GAS, CNST
• Diabetics are at increased risk of Klebsiella pneumonia
• MRSA can cause a necrotizing pneumonia that leads to complicated parapneumonic effusions. 
• The lack of anaerobic bacteria in culture does not exclude the presence of anaerobes, espcially if the fluid has a putrid odor. Empiric coverage for anaerobes should be initiatied. Common bugs include Peptostreptococcus, Fusobacterium and occasionally Bacteroides fragilus
• Don't forget tuberculous empyema, characterized by large mounts of pleural PMNs. 
• Treatment:
• Antibiotics: Should target the likely underlying cause of the pneumonia. Options for empiric therapy that cover anaerobes as well as gram + and -  include clindamycin, amoxi-clav or piperacillin tazobactam and carbapenems. 
• Sterilization of the empyema should occur within at least 4-6 wks of therapy, but therapy should be continued if there are persistent symptoms or persistent effusion as seen on imaging.
• All complicated parapneumonic effusions and empyemas should be managed with complete pleural fluid drainage. This can be done with a pig-tail or tube thoracostomy (preferred for thick loculated empyema)
• Progress should be assessed by repeat CT imaging
• Chest tubes are typically left in place until the drainage rate is less than 50mL/day and empyema cavity has closed
• If Unsuccessful, thoracics may need to be involved for a VATS (video assisted thorascopic surgery) for debridement / decortication
• Fibrinolytic agents can also be used to improve drainage of loculated effusions/empyemas. 

Cerebellar Exam

 

Yesterday we learned about how to do a neurologic exam of the cerebellum. Here is a recap for those of you unable to attend:

1) The Cerebellum 

• Coordination of volitional movements: adjusting the rate, range, force and sequence
• Motor deficits from the cerebellum are ipsilateral to the lesion, while deficits to the motor cortex of the cerebral cortex are contralateral to the lesion.
• Clinical localization in the cerebellum: The cerebellum can be divided sagitally for purposes of localization of function
• Midline: concerned with posture, locomotion, position of head relative to trunk. Midline cerebellar disease presents with disorders of stance/gait, truncal postural disturbances.
• Intermediate: Paravermal region of cerebellum. Concerned with velocity, force of volitional movements.
• Lateral: Concerned with planning of volitional movements in connection with the Rolandic region of the cerebral cortex.

2) Cardinal Signs of Cerebellar Dysfunction:

• Hypotonia
• Ataxia: defective timing of contraction of antagonistic/agonistic muscles, results in a disurbance of the smooth performance of voluntary movements.
• Dysarthria
• Abnormal ocular movements
• Tremor

3) Inspection

• Level of Consciousness
• Acute cerebellar strokes can cause raised ICP that can impair LOC
• Tone:
• Hypotonia can occur with acute cerebellar infarcts

4) Gait

• Have patient walk normally, then heel to toe (tandem gait)
• Walk is wide based, staggering, lurching.
• Lesions of the lateral cerebellum result in Patients falling towards the ipsilateral side of the lesion
• Lesions of the midline result in movements in all directions.
• Ataxia secondary to vestibular disease may appear similar (patients fall towards the affected vestibular apparatus)

5) Test of Station

• Romberg Test - Not positive in cerebellar disease (positive Romberg = patient falls). With eyes open and closed patient has a sway (towards ipsilateral side of there is a lateral lesion of the cerebellum. Visual orientation does not improve the ataxia.

6) Cranial Nerves

• Test for any bulbar abnormalities which may accompany a cerebellar stroke

7) Nystagmus

• Midline lesions: Gaze evoked nystagmus, up beat, opticokinetic, rebound nystagmus. Opsoclonus - multivectorial, fast, involuntary eye movements.
• Lateral lesions: unidirectional with fast phase towards the affected side
• Non-fatiguable

8) Speech

• Scanning, staccato, explosive speech. Unable to control volume.
• Ask the patient to take a deep breath and say "ahhhh". This tests for control of the expiratory muscles and vocal cords 
• Ask the patient to say "la, la, la" and "me, me, me" to test for rapid alternating movements of the tongue and lips.
• Ask patient to say the ABC's to assess the meter and volume of speech

9) Ataxia of the extremities:

• Ask patient to extend arms out in front and observe for tremor. Sharply tap the arms proximally and observe for oscillations of the arm as they return to baseline. The affected side has more violent oscillations.
• Test for Rebound: Ask the patient to flex their arm against your resistance, place an arm on their shoulder to protect their face. Suddenly let go of the flexed arm and observe if the patient is able to arrest the rebound of the flexed arm. Patients with Cerebellar dysfunction will be unable to do this.
• Dysmetria: abnormal excursions of movement, frequently undershooting or overshooting the target
• Tested by finger to nose testing. Must extend arm completely.
• Dysdiadochokinesia: Difficulty with rapid alternating movements
• Test with hand tapping on thigh or foot tapping
• Test with alternating fingers touching the opposing thumb.

10) Reflexes:

• Test for Pendullar reflexes with excessive sway

For more information refer to: Cerebellar exam

Nephrotic Syndrome

Today we had an excellent discussion about a 61 yo Female who presented with an acute onset of anasarca and nephrotic range proteinuria with a normal serum creatinine.

There are three major causes of nephrotic syndrome:

1) Minimal Change Disease

• Epidemiology: Most common in children, but has bimodal distribution. 
• Clinical presentation: sudden onset (days to weeks) of nephrotic syndrome. Can also have microscopic hematuria. Usually have normal serum creatinine. In elderly, often present with hypertension.
• Etiology:
• Idiopathic
• Drugs: NSAIDS (most common), antibicrobials (ampicillin, rifampicin, cephalosporins), Lithium, Penicillamine, sulfasalazine, Trimethadione, gamma interferon
• Neoplasms: Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia
• Diagnosis:
• Given the high prevalence of MCD in children, a diagnosis can often be made without a renal biopsy. 
• In adults, often a renal biopsy is needed to distinguish from other causes of nephrotic syndrome.
• Treatment:
• Very steroid responsive, 80-90% achieve complete remission. Takes longer in adults than children. up to 75% respond within 6months.
• Relapses are harder to treat, and may require cyclosporin.
• In conjuction with: Low salt diet, diuretic, ACEi

2) Focal Sclerosing Glomerular Sclerosis:

• Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
• Etiology:
• Primary FSGS: idiopathic cause of nephrotic syndrome (mediated through circulating permeability factors, increasing the permeability of the glomeruli to albumin). 
• Secondary: Viruses (HIV, Parvovirus B19, hepatitis C, EBV, CMV), drugs (IV pamidronate, anabolic steroids, interferon), obesity, lupus, reflux nephropathy, hypertensive nephrosclerosis.
• Diagnosis:
• Biopsy shows Segmental areas of mesangial collapse and sclerosis. Collapsing FSGS (HIV, iv pamidronate) characterized by collapse and sclerosis of entire glomerular tuft.
• Treatment:
• Responds to steroids, but is less responsive to steroids than MCD. For steroid resistant or relapsing disease, cyclosporine is commonly used.

3) Membranous Disease:

• Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
• Etiology: Solid organ tumours, lupus - class V lupus nephritis (does not need to be accompanied by other disease manifestations of lupus), infections (Hepatitis B, syphilis), Drugs (penicillamine, gold, NSAIDS)
• Diagnosis: 
• ANA, C3/4, Hepatitis serology, 
• Biopsy shows: Thickening of the glomerular basement membrane, in absence of hypercellularity.
• Treatment
• Control BP, ACEi, diuretic
• Prednisone +/- cyclophosphamide or cyclosporin

For more information refer to the following great articles on Nephrotic syndrome:

Nephrotic Syndrome, New England Journal of Medicine, 1998

Attending Rounds: An older patient with Nephrotic syndrome CJASN

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea here are some pearls:
1) Definition:

• Bloody Diarrhea = Colitis
• Triad of bloody diarrhea, lower abdominal pain and fever = "Dyssentry"

2) Etiology:

• Infectious: Salmonella, Shigella, Yersinia, Campylobacter, C. difficile (though rare), E. coli (enterohemorrhagic O157:H7), CMV in immunocompromised hosts. The most common causes in Toronto would be campylobacter
• Ischemic: Embolic (a. fib, cardiogenic emboli), mesenteric vein thrombosis, aortoiliac bypass, cardiopulmonary bypass.
• Inflammatory: Inflammatory bowel disease, vasculitis of the gut
• Radiation colitis

3) History:

• Exposure history: 
• Travel/sick contacts
• Food: raw beef, pork, poultry, alfalfa sprouts (E.coli), rice (B. cereus), unpasteurized dairy
• Timing of onset: less than 6hrs likely from pre-formed toxin, 8-16h think clostridium, more than 16hrs think viral or bacterial infection, if starts as diarrhea and progresses to h/a, myalgias, think listeria (especially in pregnant women)
• Medications: recent abx
• Recent hospitalizations
• Hx of IBD, radiation, immunosuppression
• Extra-intestinal manifestations of IBD
• Sexual hx

4) Diagnosis:

• Stool C + S, C. diff PCR - very sensitive and specific
• Stool O + P - not very cost effective, but reasonable in immunocompromised patients, community outbreaks of giardia or cryptosporidium, chronic diarrhea.
• Stool leukocytes - not very helpful

5) Treatment:

• Supportive!
• IV hydration, replete electrolytes (patients often have Non-Anion Gap Metabolic Acidosis initially)
• Should you treat with Antibiotics?
• Impact is modest: Decreases duration of symptoms by several days
• Consider treatment in people at risk for complications: elderly, diabetics, cirrhotics, immunocompromised
• Antibiotics are indicated for ETEC (fluoroquinolone), C. diff (metronidazole), Salmonella (flouroquinolone). Abx can also be used for severe campylobacter (macrolides or flouroquinolone)
• See the following link for Utility of antibiotics in diarrhea
• HUS: caused by the shiga toxin from E.coli O157:H7 characterized by bloody diarrhea, MAHA, thrombocytopenia, acute renal failure +/- neurologic symptoms. Antibiotics have been shown to prolong diarrhea and lead to worse outcomes. Prognosis is better than TTP.