Does my butt look firm... or inflammed?

Complications of Polymethylmethacrylate injections

1) What is it?
PMMA is a synthetic material that was first synthesized in 1902 and patented as Plexiglas in 1928. It was initially used in the medical field as bone cement but has gone on to have multiple different uses, including intra-ocular lenses and vertebroplasty. Given its smooth surface, chemical innertness and biocompatibility it has become popular as a dermal filler in cosmetic procedures. There are many commercial fillers containing PMMA, differing in terms of the size of the PMMA spheres and the suspension.


2) How does it work?
PMMA is injected into the dermis. Initially after implantation there is an acute macrophage mediated inflammatory reaction. Permanent results occur when macrophages convert into epitheliod cells that replace the suspension material with fibrin and eventually collagen. However, in a small percentage of cases (pharmaceuticals state less than 2.5%) a nodular granulomatous reaction can occur.

3) Complications:
A study out of the University of Sao Paulo documented and described 32 cases of complications due to PMMA.

• Tissue necrosis: can occur immediately. Caused by disruption of the vascular supply, by injection or compression on vessels.
• Delayed type sensitivity to bovine collagen plus PMMA, has been documented 6-24 mo post injection.
• Granulomas: occurred 6 months - 1 year post injection. Characterized by localized pain and nodules at the site of injection.
• Chronic inflammation: 1-10yr post injection. Characterized by cyclic pain and swelling.
• Local infection: can occur immediately and has been documented up to 1 yr post injection.

Some food for thought next time you consider joining a PMMA party...

Complications of PMMA injections

Autoimmune Polyglandular Syndrome

Yesterday we talked about an interesting case of a young male with a history of Type I DM and Celiac disease who presented with severe hyperkalemia (8mmol/L), hyponatremia, hypotension and non specific abdominal complaints.

With that degree of hyperkalemia and his history of multiple autoimmune diseases, the working diagnosis was primary adrenal insufficiency and possibly Polyglandular Autoimmune Syndrome type II.

1) Autoimmune Polyglandular Syndrome type I (AKA Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy APECED)

• Hypoparathyroidism
• Chronic mucocutaneous candidiasis
• Primary adrenal insufficiency (Addison's disease)
• hypogonadism
• Malabsorption and other gastrointestinal disorders

2) Polyglandular Autoimmune Syndrome type II (much more common)

• Type I DM
• Autoimmune thyroiditis, occasionally Graves disease
• Primary adrenal insufficiency
• Secondary adrenal insufficiency from autoimmune hypophysitis
• Hypogonadism
• Non-endocrine autoimmune phenomenon (vitiligo, myasthenia gravis, TTP)
• Schmidt's syndrome: primary adrenal insufficiency and autoimmune thyroid disease

Fever in the Immunosuppressed Patient

Today we talked about fever in a patient with a history of AML after completion of chemotherapy. We spoke about the importance of maintaining our natural barriers (mucosal, skin, nails) in defence of pathogens. Here are some important points we touched on:

1) Types of immunity:

• Innate: 
• Parts of the immune system able to respond to insults immediately, not reliant on antibodies or other acquired mechanisms
• Acquired:
• Cellular: Mediated largely by T cells. Important for intracellular pathogens (mycobacterium, fungal infection, viruses, some bacteria, parasites)
• Humoral: immunologic responses mediated by antibodies (from B-cells and T helper cells) Important for defence against encapsulated bacteria
• Our patient had AML with post chemotherapy bone marrow suppression and severe neutropenia. Therefore she had suppression of both her innate and acquired immune system.

2) Mucositis/Esophagitis

• Bacterial translocation: 
• Gram positives: Strep viridans and milleri. The S. milleri group can survive under low oxygen tension and is "abcessogenic"
• Anaerobes: Fusobacterium (associated with internal jugular thrombophlebitis AKA Lemierre's syndrome)
• Gram negatives: institutionalized/sick patients may develop colonisation of the Upper GI tract with lower GI tract commensals, putting them at risk of gram negative bacteremia. Consider Pseudomonas aeruginosa, Enterobacteriacea, Enterococcus.
• Fungal
• Candida
• Fluconazole: activity limited to yeasts and some endemic fungi (histoplasma, blastoomyces, coccidioides and paracoccidioides). Excellent activity against Candida albicans, but less against non-albicans.
• Itraconazoel: Broader spectrum than fulconazole. Including endemic fungi, sporothrix schenckii and aspergilus.
• Voriconazole: enhanced activity against aspergillus and other hyalohyphomycoses. Superior to fluconazole resistent C. glabrata dn C. krusei.
• Posaconazole: expanded spectrum with activity against mucorales, yeasts and molds.


• Viral
• HSV, CMV

3) Aspergillosis

• Invasive aspergillosis: Diagnosis based on culture of aspergillosus with histopathologic evidence of invasive hyphae or culture from a normally sterile site. Galactomannan or Beta D glucan assay can also be used to determine invasive aspergillosis.
• Chronic pulmonary aspergillosis: Four types: aspergilloma, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis.

Internal Medicine Potpourri!

Today we heard about a potpourri of Internal Medicine cases. Here are a few highlights:

1) Diabetic foot infections:

• IDSA Classification: Grade 1 = colonisation, no evidence of infx (clean based ulcer with granulation tissue, no purulence or cellulitis); Grade 2 = At least two signs of infection (erythema, purulence, pain, warmth, induration) and less than 2cm of surrounding cellulitis; Grade 3 = 2+ cm surrounding cellulitis, involvement of bone, tendon or deep fascia but no systemic toxicity; Grade 4= systemic toxicity.
• Microbiology: Grade 1-2 : usually gram + organisms (MSSA, Strep group A, B, C, G, enterococcus). Grade 3+ Polymicrobial: MRSA, staph, strep, gram negative bacilli (e. coli, proteus, klebsiella, ESBL, pseudomonas) and anaerobes (peptococcus, peptostreptococcus, bacteroides, fusobacterium). Risks for resistance: chronic wounds, prior hospitalization and previous abx therapy.
• Treatment: 
• Non pharmacologic: decrease pressure on wounds, good wound care.  
• Pharmacologic: (suggested regimens only, check with institution specific resistance profiles) Grade 1-2: Abx with good Gram + coverage (Cloxacillin, Cephalexin, Amoxi-clav), if MRSA possible add Septra or Vancomycin. Grade 3: Add aerobic Gram - coverage and anaerobic coverage (Cipro + Clinda, moxifloxicin, cephalosporin + Clinda). Grade 4: consider Pipericillin/tazobactam or a carbapenem. 
• See the following article for a review on the microbiology and treatment of Diabetic foot infections: Diabetic foot infections

2) NSAIDS and PUD

• The risk of causing GI bleeding is nto equal amongst all NSAIDS. A meta-analysis of controlled trials   of commonly prescribed non-selective NSAIDs found that the risk of highest in indomethacin (RR 2.25), then naproxen (RR1.83), diclofenac (RR1.73), ibuprofen (1.43) and meloxicam (RR 1.24).
• The latest trend is to prescribe an NSAID with a PPI (ie. Vimovo has naphroxen and esomeprazole) However, there is evidence for worsening NSAID induced small bowel injury, due to the changes in small bowel micro-flora with PPI use. So ultimately, NSAID use should still be limited in patients at risk of GI complications.

3) DKA

• While serum K+ may be normal, patients have low total K+. Must treat K+ and maintain greater than 4. Best way is orally (may need to place NG tube)
• Insulin IV to treat the Anion Gap
• Fluids to treat the hyperglycemia
• Patients are usually phosphate deficient, however trials looking at repletion of phosphate in DKA showed no difference in duration of DKA, rate of AG improvement or morbidity/mortality. Hypophosphatemia of less than 0.32mmol/L can cause hemolysis, rhabdomyolysis, myoglobinuria (but is rare). Therefore consider treating only if Phosphate is less than 0.3.

Unusual Causes of Upper GI Bleed

Today we talked about UGIB with Dr. Ho Ping Kong. Here are some key points we talked about:

1) Most common causes of UGIB:

• Peptic Ulcer disease - 55%
• Variceal - 14%
• Arterial, venous and other vascular malformations - 11%
• Mallory Weiss - 5% (although Dr. HPK would disagree)
• Erosions - 4%
• Malignancy - 4$
• Other - 11%

2) Unusual causes of UGIB:

Watermelon Stomach

•  
• Dieulafoy's lesion: Dilated submucosal vessel that is usually located in the antrum of the stomach, but can be found in the esophagus and duodenum. Thought to be congenital. As the artery is not surrounded by stomach muscle, it can become dilated. The artery can bleed (triggered by NSAIDs?) resulting in profuse bleeding, that is often self limited.
• Gastric Antral Vascular Ectasia (GAVE): AKA Watermelon stomach. Characterized by longitudinal rows of ectatic/sacculated mucosal vessels running from the antrum to the pylorus. Can be idiopathic, but also associated with cirrhosis and systemic sclerosis. Most common presentation is that of slow, chronic blood loss and iron deficiency anemia. 
• Vascular anomalies: Osler-Weber-Rendu or Hereditary Hemorrhagic Telangiectasia, Ehrlos Danlos, CREST, Klippel-Trenaunay-Weber syndrome.
• Portal Hypertensive Gastropathy: Occurs in patients with cirrhosis and portal hypertension. Mucosa has a snakeskin like appearance with a fine white reticular pattern and areas of pink mucosa.
• Hemobilia: Bleeding from the hepatobiliary tract. Usually occuring after hepatobiliary instrumentation.
• Hemosuccus Pancreaticus: Bleeding from the pacreatic duct. Usually occurs with pancreatic pseudocysts or tumours that erode into adjacent arteries.
• Aortoenteric Fistulas: Usually secondary to ulcers/tumours. Arteries affected include aorta, gastroduodenal artery.
• Cameron lesions: Ulcers in a hiatus hernia
• Tumours: Lymphoma, Kaposi's sarcoma
• Secondary Angiodysplasia: End stage renal disease, aortic stenosis and Heyde's syndrome

3) Unusual causes of PUD:

• H. Pylori (~61% of DU and ~63% GU) and NSAIDs account for the majority of peptic ulcer disease.
• Gastrinoma: Zollinger-Ellison Syndrome: Non-beta cell islet tumour of the pancreas associated with acid hypersecretion and multiple peptic ulcers. Can occur sporadically or in association with MEN I (hyperparathyroidism, pancreatic tumours and anterior pituitary tumors).
• Systemic mastocytosis: Secondary to increased circulating histamine
• Carcinoid tumours: Also secondary to increased circulating histamine
• Other infections: HSV-1, CMV
• Stress ulceration: Hospitalized/critically ill ICU patients
• Sarcoidosis
• Crohn's Disease

4) HPK Classic (Couldn't leave this out)

Bob Marley leads to Rastafari leads to Rasmussen's Aneurysm 

Rasmussen's Aneurysm: A pulmonary artery aneurysm adjacent to or within a tuberculous cavity. Can cause fatal hemoptysis

.

Syncope

 

Syncope is one of the most common problems encountered in the emergency department. The greatest challenge is determining who should be admitted for inpatient investigations and who can be investigated as an outpatient. 

1) What is it: Transient, self limited, loss of consciousness.

2) How is it classified:

 3) Approach to Diagnosis:

• The cause of a syncopal event is often in the HISTORY
• The history should focus on the following:
• Circumstances surrounding episode: Position (supine, sitting, upright); activity (micturition, defecation, unpleasant experience, exertion); predisposing factors (warm, crowded etc.)
• Prodromal symptoms: Nausea, vomitting, diaphoresis, aura, palpitations or lack of prodorome
• Eye witnesses: Abnormal posturing, movements of limbs, incontinence etc.
• After the event: New weakness, confusion, level of consciousness
• History: Previous events, family hx of sudden cardiac death, hx of coronary artery disease, structural heart disease.
•  Historical features worrisome for cardiac syncope:
• Lack of prodromal symptoms, syncope with exertion or supine. Syncope associated with palpitations.
• Hx of structural cardiac disease
• Abnormal ECG (sinus bradycardia, Mobitz II or 3rd degree, intraventricular conduction delay (QRS >0.12sec)
•  Boston Syncope Criteria: Patients meeting any one of the following criteria should be admitted for further investigation:
• Signs and symptoms of ACS
• Worrisome cardiac history (hx of CAD, CHF, hx VT/Vfib, pacemaker/ICD, antiarrhythmic medications)
• Family hx of sudden death
• Valvular heart disease on hx of exam
• Signs of conduction disease
• Volume depletion
• Perisistent abnormal vital signs in the ED
• Primary CNS event.

4) Investigations:

•  Cardiac investigations:
• Telemetry
• ECHO
• Exercise test
• Ischemia evaluation
• If the above is normal, consider the following tests as an outpatient: 
• If symptoms are frequent Holter monitor 24-48hr
• If symptoms are infrequent consider Implantable loop recorder
• Tilt table testing if hx suggestive of neurocardiogenic syncope

See the following for more information:
Boston Syncope Criteria
European Heart Journal guidelines on treatment of syncope

Delirium Tremens

CIWA protocol

Delirium Tremens

Last night we had, as Dr. McNeely put it, "a tsunami of alcoholics". Here are some pearls on Delirium Tremens or the "Rum Fits"

1)What is it: It is a state of severe psychomotor agitation and sympathetic overdrive in chronic alcoholics who have been abstinent for ~ greater than48-96hrs, but can occur up to 7-10 days since the last drink. It also happens to be the name of a brand of Belgian golden ale as seen above!

2) When to suspect it:

• Prolonged daily alcohol consumption
• Symptoms of withdrawal even while serum etOH levels are still elevated
• Prolonged period of abstinence
• Comorbidities
• Increasing age
• History of DTs

3) What to expect:

• Psychomotor agitation: anxiety, delirium, tremor, hallucinations, seizures,
• Autonomic dysfunction: hyperthermia, hypertension, tachycardia, tachypnea, diaphoresis, midriasis
• Seizures: Alcohol withdrawal seizures can occur within 12-48 hours of the last drink, and can occur without DTs. They are tonic clonic, and occur as a single seizure or a brief flurry of seizure activity. If seizures are prolonged or continue for >6 hr period other causes of seizures should be investigated (i.e. intracerebral hemorrhage). 

4) How to Treat:

• Benzodiazepines are the mainstay of treatment
• For patients in the acute phase of alcohol withdrawal treat with diazepam. 
• Diazepam 10-20 mg PO Q1H x 3
• If unable to tolerate PO Diazepam IV 2-5mg Q5-10 min until appropriate level of sedation is achieved.
• Rather than keeping patients sedated it is better to practice symptom based treatment with the CIWA protocol
• When to start CIWA: For any patient at risk of alcohol withdrawal who has been abstinent for <12 hrs="hrs" li="li">
• When to stop CIWA: For any patient with a CIWA of less than 10 x 3 consecutive evaluations
• Hallucinations
•  Can treat with Haloperidol (watch the QTc)
• Metabolic disturbance
• Treat electrolyte abnormalities, Mg, Phos, K+
• Treat malnutrition: Thiamine 100mg IV daily x 3 and folate
• IV rehydration
• Patients can have arrhythmias and should be on telemetry
• Refer to the following link regarding treatment of alcohol withdrawal: CIWA protocol

Hyponatremia

Hyponatremia is the most common electrolyte abnormality encountered in the hospital. It primarily signifies a problem with water, not salt.

Etiology: Net gain of electrolyte free water relative to the body's stores of Na and K. This can occur in three volume states:

1) Hypovelemic State: ADH is appropriately released resulting in the retention of water in the kidneys. There is relatively more water retention than sodium retention resulting in hyponatremia. The urine osmolality will be high and urine sodium will be low. Thiazide diuretics are also common culprits of chronic hyponatremia.

2) Euvolemic State:

• SIADH: ADH is inappropriately released by many mechanisms including pain response, nausea/vomitting, CNS disturbance, pulmonary disease, medications (anti-depressants, anti-convulsants, MDMA/ectsasy)
• Tumour producing ADH
• Endocrine abN (hypothyroidism, adrenal insufficiency)
• Low solute diet (tea and toast, beer potomania)
• Psychogenic polydipsia.

3) Hypervolemic State: Low effective circulating volume i.e. cirrhosis, heart failure.

Severity:
The degree of severity is inversely proportional to the serum Na and the time frame over which the change occurred. The risk of hyponatremia is inversely proportional to the Serum Na, with serum Na less than 120mmol/L considered severe. Symptoms are non-specific, including lethargy, headache, confusion, seizures and decreased LOC. Patients with seizures and decreased LOC, secondary to low Na, should have their serum Na corrected quickly (see treatment below). However patients with chronically low serum Na, do not need to be corrected quickly and may in fact be harmed by over correction.

Patients with chronically low serum [Na] develop shifts in the intracerebral osmoles to coompensate for the chronically low serum [Na]. Therefore, if a rapid correction of serum [Na] occurs, this can result in a sudden shift of water extracellularly, putting patients at risk of osmotic demyelinating syndrome (ODS) or cerebral pontine myelinolysis (CPM). Patients who are elderly, malnourished and hypokalemic are at the highest risk. In the case of rapid correction (8mmol/day or more), the serum Na must be decreased quickly to prevent the development of ODS/CPM. Treatment includes administering hypotonic IV fluids and giving DDAVP to increase serum ADH.

Diagnosis:
1) Start by confirming hyponatremic hyponatremia by doing a serum osmolality. Rule out hypertonic hyponatremia caused by other osmoles (hyperglycemia, mannitol)

2) Assess volume status: hypervolemic, hypovolemic, euvolemic

3) Confirm volume status with urine lytes:

• Hypovolemic: High urine osmolality greater than 300mOsm. Low excretion of urine Na less than 20. 
• Euvolemic: Normal urine Na, normal urine osmolality.
• Keep in mind if pt is on Lasix, urine Na may be high!

Treatment of Hyponatremia:
1) Severe Hypo Na: Treat with hypertonic saline 3% (513 mOsm). Give 100cc 3%NS over 10 minutes, this should increase serum [Na] by 2meq. This can be repeated twice every 10 minutes. Pateints should be treated until symptoms resolve (i.e. seizures). Furosemide can be given reduce volume expansion and prevent shutting off of ADH and diuresis.

2) Non-severe hypovolemic HypoNa: A safe range for improving sodium is 6-8mEq/24 hrs. Patients should be monitored for urine output, repeat serum lytes and urine lytes Q4hr as they receive IV fluids. A sign of aquaresis is the sudden production of large amounts of dilute urine. If this occurs, to prevent rapid correction of serum [Na], DDAVP can be given 2-4mcg IV. Some insititutions advocate for giving DDAVP up front, however as long as close care is taken to detect aquaresis early, giving up front DDAVP can be avoided.

3) SIADH = restrict fluid to less than 1.5L per day, and consider salt tabs.

Please refer to the following recently published article on Hyponatremia in JASN: http://jasn.asnjournals.org/content/23/7/1140.full.pdf+html?sid=c14ec703-91e2-4d5e-966e-eef3e9aa8ac5

Nephrotic Syndrome

Today we talked about a patient presenting with bilateral leg edema and proteinuria. This brought up the topic of Nephrotic syndrome:

1) Nephrotic Syndrome:

• Characterized by nephrotic range proteinuria (usually more than 3 g/day), edema and hypoalbuminemia (<3g also="also" and="and" associated="associated" g--="g--" hypercoagulable="hypercoagulable" hyperlipidemia="hyperlipidemia" state.="state." with="with">
• Hyperlipidemia: Triglyceride rich lipoproteins increased in nephrotic syndrome due to decreased catabolism. This is likely due to decreased binding of lipoprotein lipase (LPL) to endothelial cells secondary to the reduced oncotic pressure.
• Hypercoagulable state: Likely secondary to an imbalance between naturally occuring pro-coagulant/pro-thrombotic factors and anti-coagulant and anti-thrombotic factors. Likely multifactorial, related to increased urinary losses of anti-thrombin, Protein C, Protein S and increased levels of fibrinogen. See this paper for a review of hypercoagulability and nephrotic syndrome
• Increased susceptibility to infections: unclear etiology, but may be related to urinary losses of IgG.

2) Etiology

• Focal segmental glomerulosclerosis: common cause of idiopathic nephrotic syndrome in adults
• Reflux nephropathy
• Nephron loss: surgical or congenital
• Intraglomerular hypertension from primary renal vasodilation: Diabetes, sickle cell disease
• Obesity
• Interferon

• Minimal change disease: Most common cause in children, also occurs in adults.
• Drugs: NSAIDs, antimicrobials (ampicllin, rifampin), penicillamine, lithium, sulfasalazine
• Paraneoplastic phenomena: Hodgkin's lymphoma, NHL, leukemia, rarely solid tumors
• Infectons: TB, syphilis, Hep C, HIV, erlichiosis, mycoplasma, echinococcus
• Systemic diseases: Diabetes, SLE, PCKD, HIV
• Allergy
• Membranous nephropathy
• Malignancy, typically solid tumor (GI, prostate, lung) and less frequently heme malignancy
• Infections: Hepatitis B/Hepatitis C, schistosomiasis, malaria, syphilis
• Autoimmune disease: SLE (lupus nephritis type V)
• Drugs: NSAIDs, penicillamine, 

• Amyloidosis
• AL/primary amyloid: Light chain dyscrasia where fragments of monoclonal light chains form amyloid fibrils.
• AA/ Secondary amyloid: Secondary to chronic inflammation where the acute phase reactant serum amyloid A forms amyloid fibrils. Occurs for example in Rheumatoid Arthritis or osteomyelitis.
• In this case, urine dipstick will be negative and serum albumin is normal.