Today, we talked about a middle aged man presenting with acute onset of abdominal pain and weight loss, found to have a consolidation on chest imaging, low SAAG ascites, and a nodular omentum, work up revealing disseminated cocci! For more cases like this, check out http://www.humandx.org. If you’d like to hear some expert diagnosticians take a crack at this case and learn from their reasoning, check out thecurbsiders.com.
- Patients with immunosuppression, pregnancy, and DM2 are at risk of developing disseminated cocci.
- The most common manifestation of cocci is pneumonia which can be consolidative, nodular, or cavitary. Other manifestations include the skin (erythema nodosum and erythema multiforme), joints (arthralgias, vertebra, osteo), meningitis, SSTI, and visceral organs (rare).
- Cocci should be on your differential of infections that can cause eosinophilia and a low SAAG ascites.
Approach to eosinophilia
- Neoplasm ⇒ hypereosinophilic syndrome, T cell lymphoma, hodgkins lymphoma, solid organs (cervical, ovarian, gastric, colon, and urothelial cell carcinoma)
- Allergies ⇒ atopy, medication induced
- Adrenal insufficiency ⇒ rare cause
- Connective tissue disease ⇒ EGPA (formerly known as Churg Strauss), RA
- Parasites: strogyloides, toxocara, lymphatic filariasis, isospora, dientamaeoba, sarcocystis (note Giardia does NOT cause eosinophilia)
- Viruses: HTLV, HIV
- Fungi: aspergillus (ABPA), cocci, paracocci, histo, crypto
- Primary eosinophilic syndromes (typically single organ involvement of eos, may not have blood eosinophilia) ⇒ eosinophilic fasciitis, eosinophilic cellulitis
Differential for ascites based on SAAG
- Peritoneal carcinomatosis
- Infections (tuberculosis, bacteria, fungi including cocci, schistosomiasis)
- Biliary ascites
- Portal HTN
- Liver (cirrhosis, acute failure, alcoholic hepatitis, budd chiari, mets)
Coccidioidomycosis: Refer to this prior post on our blog for more details.
- Airborne fungal infection transmitted by cocci immitis and cocci posadasii
- Geographic distribution is southwest US and central valley
- Most common time for transmission is summer and fall seasons
- Risk factors for developing severe disease
- Immunosuppression (HIV with CD4 <250, steroids, chemo)
- DM2 (more likely to develop cavitary disease)
- Clinical manifestations
- Incubation period is 7-21 days
- Primary manifestation is CAP
- Other manifestations
- Skin: erythema nodosum and erythema multiforme
- Joints: arthralgias (desert rheumatism), osteo of joints and vertebrae
- Visceral organs and omentum (rare)
- Imaging (CXR can be normal in 50% of patients)
- Cocci EIA to screen
- Cocci immunodiffusion and complement fixation to confirm
- Immunocompetent and minimal symptoms? No treatment, most resolve spontaneously
- Severe disease/disseminated
- First line is fluconazole or itraconazole
- If no response, can try posaconazole
- Last resort is amphotericin B
- Duration of treatment can be up to a year
- Repeat anti-coccidioidal Abs in 2-4 weeks after starting treatment to ensure treatment response
Joe presented the case of a young man from Mexico with unknown immunization history who presented with acute onset of AMS, fevers, and a progressive vesicular rash, diagnosed with primary varicella infection (chickenpox!), now in the ICU with varicella pneumonia and likely varicella vasculitis induced stroke.
- Vaccinate your kids!
- Two main VZV presentations are primary infection (chickenpox) and reactivation (shingles, disseminated zoster in immunocompromised individuals)
- Varicella rash presents as vesicular lesions at varying stages. Vesicular lesions at the same stage of development are concerning for smallpox.
- The most common complication of primary VZV in adults is pneumonia. Treatment is with IV acyclovir.
- The most common neurologic complication of primary VZV is encephalitis. No approved therapy exists.
- Isolation precautions for shingles is contact. For disseminated zoster or chickenpox, make sure you patient is on contact and airborne precautions.
Differential for fever, rash, and pharyngitis:
- Mono (due to EBV, CMV, toxo, HHV6)
- Acute HIV
Fever and rash emergencies:
- Subacute bacterial endocarditis
- Rocky Mountain Spotted Fever
- Necrotizing fasciitis
- Toxic epidermal necrolysis
- Toxic shock syndrome (staph aureus or GAS)
Varicella zoster (VZV)
- Primary infection – chickenpox
- Clinical manifestations:
- Prodrome of fever, malaise, pharyngitis, loss of appetite
- Rash is often pruritic and occurs in successive crops over days (new vesicle formation stops after 4 days). Vesicular lesions at varying stages on an erythematous base on the trunk, face, and extremities.
- send swab (from ulcer base) for HSV PCR and DFA. These have quick turn around time and high sensitivity. Viral culture takes weeks and is less sensitive.
- Most common complications
- Children: skin infection
- Pneumonia (1/400 cases) with a mortality of 10-30%. In people requiring mechanical ventilation, mortality reaches 50%.
- Risk factors for pneumonia development are cigarette smoking, pregnancy, immunosuppression, and male sex.
- Develops 1-6 days after the appearance of rash
- CXR usually with diffuse bilateral infiltrates with possible nodular component in early stages
- Prompt administration of acyclovir has been associated with clinical improvement
- Encephalitis: acute cerebellar ataxia (more common in children), diffuse encephalitis (more common in adults)
- No proven therapy once encephalitis occurs. Acyclovir has been used with anecdotal success
- Transient focal deficits
- Aseptic meningitis
- Transverse myelitis
- Vasculitis (medium to large vessel vasculopathy)
- More common in immunocompromised hosts and frequently fatal
- Diarrhea, pharyngitis, otitis media
- For healthy children <12 ⇒ nothing
- For adults
- if no complications, then oral valacyclovir (1g TID) or acyclovir (800 mg 5 times/day)
- if immunocompromised ⇒ treat with IV acyclovir if active lesions present (10mg/kg q8h)
- if complications
- acyclovir IV 10mg/kg q8h for 7-10days
- contact and airborne precautions!
- Reactivation – shingles
- Clinical manifestations –
- Rash – most common location is thoracic and lumbar dermatomes
- Localized, painful and restricted to a dermatome
- Disseminated if > 3 contiguous dermatomes or 2 dermatomes on separate parts of the body, painful
- Acute neuritis – 75% of patients have pain/burning/throbbing prior to onset of rash
- Complications in immunocompetent hosts –
- post-herpetic neuralgia (most common), superficial skin infections, ocular complications (acute retinal necrosis and zoster ophthalmicus), motor neuropathy, meningitis, Ramsay hunt syndrome (zoster oticus)
- For patient with localized disease presenting <72 hours after clinical symptom onset, treat with oral acyclovir, valacyclovir, or famciclovir
- For patient with localized disease presenting >72 hours after disease onset, then monitor
- Pregnant women, treat with acyclovir
- Disseminated disease, treat with IV acyclovir
Adam presented a case of a 32yo woman with an extensive alcohol history presenting with seizure in setting of recent cessation of alcohol. Pt has also been complaining of weakness in her legs to the point she could no longer walk, worsening vision, and urinary incontinence for the past few months. Per her family, she only ate one meal a day and she was quite picky in terms of her diet.
She was treated for alcohol withdrawal and delirium tremems. When she was stabilized, her neurological exam was concerning for significant weakness in proximal and distal upper and lower extremities, paresthesia, dysmetria, and hyporeflexia. An EMG was done which revealed peripheral polyneuropathy. This constellation of symptoms (alcohol, poor nutrition, polyneuropathy) is consistent with… Beriberi!
- Developing countries
- Extreme poverty
- Displaced populations, refugees
Common Risk factors
- Poor nutrition
- Weight loss surgery
- Long term TPN
Presentation of Thiamine Deficiency
- Wet beriberi
- Heart failure due to thiamine deficiency (high out heart failure)
- Vasodilation, tachycardia, widened pulse pressure, diaphoresis, lactic acidosis, peripheral edema
- Dry beriberi
- Peripheral polyneuropathy, affects predominantly lower extremities, both sensory and motor deficits, can lead to muscle wasting, loss of deep tendon reflexes, paralysis of the lower legs, mental confusion, speech difficulties, nystagmus
- Wernicke Korsakoff
- Wernicke Encephalopathy: triad of encephalopathy (disorientation, inattentiveness indifference), gait ataxia, and oculomotor symptoms (nystagmus, lateral rectus palsy, conjugate gaze palsies)
- Triad only seen in 1/3 of patients, most only have around 2.
- Diagnosis: Clinical but there is a proposed Caine Criteria
- Dietary deficiency
- Oculomotor abnrl
- Cerebellar dysfunction
- Encephalopathy or memory impairment.
- Korsakoff Syndrome: Memory loss, confabulation, +/-hallucinations
- Chronic inadequate intake of thiamine (vitamin B1) leading to degeneration of the peripheral nerves, thalamus, mammillary bodies, and cerebellum.
- Heart may become dilated, may lead to a high output heart failure
- Vasodilation can occur causing edema
- Clinical history
- Thiamine level
- Clinical improvement with thiamine administration
- CT: May see classic atrophy in the mammillary bodies in Wernicke Korsakoff, highly specific.
- DO NOT GIVE GLUCOSE 1st, thiamine must be repleted first or else glucose infusions may worsen symptoms. Alcoholics should receive IV thiamine, at least 100mg, before receiving any IV glucose solutions.
- Nutritional support, thiamine replacement
- Fix underlying cause (i.e. alcohol)
- Thiamine initially is given in very high doses if treating, 500mg IV 3 times daily for 3 days, then 250mg daily for 3-5 days, then transition to 100mg PO daily.
- Most will have a degree of neurological deficits despite treatment.
Jonathan presented a case of a 39yo M with no significant medical history, presenting with 1 month of non-improving dry cough, dyspnea on exertion, subjective fevers, and leg weakness. His CK was significantly elevated on admission to 27k, and CXR revealed peri-hilar lung base opacities which could represent pneumonia. His exam was significant for debilitating proximal muscle weakness (distal strength was intact!) with hyporreflexia. Ultimately Anti-Jo1 antibodies returned positive, and CT Cx revealed predominantly lower lobe GGO without evidence of honeycombing or traction atelectasis. This constellation of findings (myopathy, lung pathology, anti-synthetase antibody positivity) is consistent with Anti-synthetase syndrome!
- Up to 30% of patients with DM or PM will have this constellation of clinical findings, terms Anti-Synthetase syndrome.
- More acute onset of the following:
Presentation: Often acute
- Constitutional symptoms i.e. fever
- Raynaud’s phenomenon
- Mechanic hands
- Non-erosive arthritis
- ILD: Often severe and rapidly progressive, frequently predominates other symptoms
- Cardiac arrhythmias or ventricular dysfunction
- Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
- Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
- Anti-U1 RNP
- Anti PL-7 & PL12 (seen in pts with predominantly ILD sx, often very severe)
- If antiRo or ANA present, suspect more of an myositis associated ILD
- Most common findings are traction bronchiectasis, GGO
- Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.
- Often requires multiple immunosuppressives for symptomatic control.
- First line: Corticosteroids, monotherapy associated with more frequent lung disease recurrence
- Other agents often added i.e. azathioprine, mycophenolate, tacrolimus, rituximab, cyclophosphamide.
- Chronic steroids: osteoporosis, PJP prophylaxis if > 20mg > 1 month
- Hep B reactivation
- Azathioprine: Check TPMT levels!
- Not associated with inc risk of malignancy
- Anti PL7 and PL12 are associated with more aggressive ILD, and worse prognosis.
- Presence of Anti-Jo1 and arthritis/myositis are actually good prognostic indicators.
- Single center study: 10 year survival for Anti-Jo1 was 70%, vs 49% for non-Jo1
Jihong presented a case of a 57yo woman with no medical history, who was in her usual state of health until 2 weeks ago when she started complaining of a sore throat. The day prior to presentation, the patient’s roommate saw her “sleep walking” and not acting like herself. When her cousin saw her, she immediately brought her to the hospital because the patient was becoming increasingly more confused and agitated. She was ultimately diagnosed with bacterial meningitis secondary to strep pneumo.
Acute Bacterial Meningitis
- Developed Countries
- Community acquired
- Streptococcus pneumoniae (most common)
- Neissseria meningitidis
- Listeria monocytogenes (age > 50, immunodeficiency)
- H. influenzae Type B: less likely given HiB immunization but rates of vaccination are declining…
- Healthcare acquired
- Associated with neurosurgery (i.e. drains), skull trauma.
- Usually staphylococci and GNR
- Risk factors
- Asplenia (encapsulated organisms, H.influ, strep)
- Usually quite acute and patients are usually ill appearing
- Headache (usually generalized, severe, seen in most patients) + Classic Triad:
- Fever (95%, often > 38, others might be hypothermic)
- Nuchal rigidity (Also present in most patients, 88%)
- Encephalopathy (78%)
- Only 44% of patients will have all 3 triad
- More variable and subtle presentation the older you get
- Other findings
- Seizures (inc risk in Listeria)
- CN palsies (inc risk in Listeria)
- Cerebral infarction
- Petechial rash, arthritis (Neisseria meningitidis)
- Physical Exam: Brudzinski and Kernig: Not sensitive at all but quite specific. Jolt accentuation is more sensitive but less specific (horizontal rotation of the head 2-3 times per second causing a headache) but overall still quite poor in terms of both.
- Clinical history
- Low glucose
- High WBC, usually 1k – 5k, typically > 80% neutrophils
- Protein > 200mg/dL
- Glucose < 40mg/dL, or CSF:serum glucose ratio of < 0.4, the lower the worse)
- 99% PPV if any one of these are present: CSF glucose < 34, protein above 220, and WBC > 2000
- Some data suggesting using CSF lactate
- WBC can be falsely elevated in traumatic tap or underlying head trauma (i.e. prior SDH)
- Correction for traumatic tap: subtract 1 WBC for every 500-1500 RBC in the CSF, just use 1000 to remember easier.
- Blood + CSF cultures
- When to CT first
- Do CT first if the patient has the following:
- Focal neuro deficits
- Immunocompromised (HIV, transplant, etc)
- H/o CNS mass, stroke, focal infection
- Otherwise, ok to go straight for the LP, but LP is contraindicated (but not absolute) under these circumstances:
- PLt < 50
- INR > 1.4
- Lovenox, please hold at least 12 hours in advance
- Paraspinal abscess
- Empiric antibiotics, should not wait after LP to start!
- Start ASAP, don’t wait for the LP
- Most community acquired meningitis: Vancomycin and Ceftriaxone (2g Q12H) should suffice
- Age > 50 adults or immunocompromised: Add ampicillin 2g Q4H for Listeria coverage
- Community and immunocompromised: substitute CTX with cefepime
- Healthcare associated: Vancomycin, cefepime or carbapenem class with pseudomonal coverage
- PCN allergy: Can use Vanc, moxifloxacin, and Bactrim (Listeria coverage)
- Studies have shown improved neurological outcome with dexamethasone prior to abx, give dex 10mg IV q6H for 4 days.
- Start before Abx
- Also potentially reduces risk of post-infectious neurological complications.
- Most of the data is from management of pneumococcal meningitis, some have suggested that dex can be DC if another cause is diagnosed.
- < 60 yo: ~ 17% mortality
- 37% mortality in > 60
- Staph aureus: 43% mortality
- Seizures, focal neuro deficits, coexisting medical conditions, high CSF pressure, older age, coma, low CSF:serum glucose ratio tend to be associated with poor prognosis
- Post-infectious neurological complications
- As high as 15-22% in kids
- Up to 1/3 in adults
Today, we reviewed some of the hottest and potentially practice changing articles of 2018. This is by no means an exhaustive list and meant to encourage debate and tickle your fancy for more!
1. Aspirin for primary prevention of cardiovascular disease?
Bottom line: no net benefit in primary prevention of cardiovascular disease.
- ARRIVE: 12000 middle aged (mean age 64), non-diabetic participants with moderate ASCVD risk (>20%) randomized to receive aspirin 100 mg or placebo for primary prevention and followed for 5 years. Found that ASA showed no reduction in major adverse cardiovascular events or mortality, but a 2-fold higher risk of bleeding.
- ASCEND (aspirin): 15000 middle aged (mean age 63) diabetic participants randomized to aspirin 100 mg vs placebo for primary prevention of CVD and followed for 7 years. Authors found a 12% reduction in major adverse cardiovascular events with ASA but a 29% higher risk of bleeding.
- ASPREE: 19000 older patients (median age, 74) regardless of other risk factors randomized to ASA 100 mg or placebo and followed for 5 years. Study found that patients who received ASA had a 14% higher all cause mortality, no decrease in the rate of adverse CVD, and no change in disability-free survival.
2. Omega-3 for primary prevention of cardiovascular disease?
Bottom line: potentially beneficial at really high doses in patients with CV risk factors
- VITAL: 26000 middle aged (mean age, 67) people without CV disease were randomized to receive fish oil (1g) or placebo and followed for ~5 years. Study found similar rates of primary endpoint (nonfatal MI, stroke, or CV-related death) and all cause mortality in the two groups and a small but significant decrease in the incidence of MI in the fish oil group (1.1% vs 1.5%).
- ASCEND (fish oil): same study population as ASCEND for aspirin, also looked at using 1g fish oil or placebo and followed patients for ~7 years and found no difference in the risk of major adverse cardiac events.
- REDUCE-IT: 8000 participants with controlled LDL but elevated triglycerides, randomized to receive 2g of a different fish oil (icosapent ethyl as opposed to the eicosapentaenoic acid plus docosahexaenoic acid used in the previous two trials) vs placebo and followed for 5 years. Study found a 25% reduction in risk of major cardiovascular events. Caveat is high dose used at this formulation is very expensive and the study was funded by Amarin Pharma.
3. VTE prophylaxis in hospitalized patients
Bottom line: High rates of inappropriate use of pharmacologic VTE prophylaxis. Use padua score before prescribing VTE prophylaxis.
- Grant et al. JAMA Intern Med 2018: retrospective study of 45000 non-ICU patients hospitalized for > 2 days found that prophylaxis (pharmacologic or mechanical) was prescribed for 78% of low-risk patients. 27% of high risk patients with contraindications to pharmacologic prophylaxis still received it, and 22% of high risk patients did not receive prophylaxis.
4. Is there such a thing as too much oxygen?
Bottom line: higher rates of mortality associated with liberal use of oxygen in hospitalized patients.
- Chu et al. Lancet 2018: Meta-analysis of 25 randomized trials on 16000 hospitalized patients treated with liberal (median FiO2 0.52) vs conservative (median FiO2 0.21) supplemental oxygenation found that at 30 days, the relative risk of death was significantly higher in the liberal oxygenation group.
5. Plavix + ASA for TIA or minor stroke?
Bottom line: Starting DAPT within 12 hours of symptom onset (likely for 30 days) in patients with high risk TIA or minor ischemic stroke reduces 90 day stroke incidence but increases bleeding rates.
- POINT: Followed the earlier CHANCE trial in a Chinese population that showed DAPT for 21 days after TIA or minor stroke reduced stroke recurrence at 90 days without a difference in bleeding rates. POINT randomized ~5000 patients to DAPT for 90 days vs ASA alone in a primarily white patient population and found lower rates of recurrent stroke but higher rates of bleeding. Majority of stroke reduction occurred during the first 7 days after stroke and extended for 30 days whereas the bleeding rates were stable throughout the 90 day follow up period.
6. Steroids in septic shock?
Bottom line: Steroids might be beneficial in high risk patients with refractory septic shock.
- Rochwerg B et al. Crit Care Med 2018: Meta-analysis of 42 randomized trials with >10000 patients receiving steroids vs none in septic shock found a 2% relative reduction in 30-day mortality with steroids which was not statistically significant, and a similar reduction in mortality at 60 days to 1 year which reached significance (NNT 50). Reversal of shock at 7 days occurred more frequently in the steroid group (NNT 10) but mild-to-moderate adverse events also occurred more frequently in this group (hyperglycemia, hypernatremia, and neuromuscular disease).
7. Is it safe to discharge to home from the ICU?
Bottom line: patients admitted to the ICU for substance-related disorders, seizures, or metabolic derangements may be ok to go home from the ICU.
- Stelfox et al. JAMA 2018: retrospective cohort study of 6700 adult patients admitted to ICUs in Canada, 14% of whom were discharged to home, found that 30 day hospital readmissions and ED visits and 1 year mortality rates were similar in those discharged from the ICU vs wards. Those discharged home were typically younger and more likely to have been admitted due to overdose, seizure, substance withdrawal, or metabolic derangements.
8. NS vs LR?
Bottom line: balanced crystalloids (like LR) are associated with fewer adverse events than normal saline in hospitalized patients.
- SMART: 16000 patients admitted to the ICU were randomized to NS or a balanced crystalloid (majority received LR). Study found that more patients in the NS group reached the composite outcome of major adverse kidney events (death, renal replacement therapy, or doubling of creatinine at discharge) vs those who received balanced crystalloids.
- SALT-ED: 13000 patients admitted from the ED to non-ICU beds were randomized to NS vs a balanced crystalloid (majority received LR). Study found similar rates of primary outcome of hospital-free days but a higher rate of adverse kidney events within 30 days than the NS group.
Richard presented a patient from China with a history of diabetes not on medications who presents to the hospital with 4 days of lip swelling. He had a pimple just inferior to his nostrils, which he popped the day prior to onset of symptoms. He was feeling fine and he initially thought it was an allergic reaction after his lips became swollen and pruritic. His vitals were normal, but notable upper lip swelling and surrounding erythema were noted. Ultimately he underwent I&D after CT revealed gas within the soft tissues consistent with a necrotizing soft tissue infection. Cultures turned out to be hypermucoid klebsiella!
Risk Factors for necrotizing soft tissue infection
- Chronic disease
- Immunosuppressive drugs (eg, prednisolone)
- Age > 60 years
- Peripheral vascular disease
- Renal failure
- Underlying malignancy
- Precipitating events (both traumatic and non-traumatic)
- Traumatic: Surgery, procedures, acupuncture, IVDU, penetrating injuries
- Non-traumatic: Soft tissue infection, childbirth
- Pt in general are acutely ill.
- Most cases involve the limbs, perineum, or trunk. Head & neck involvement are only seen in 5% of cases
- Type A Nec Fas: Most common, polymicrobial
- Type B Nec Fas: Less common, monomicrobial
- In general, the organisms involved in nec fas are:
- Strep (group A) & staph (most common
- Gram negatives i.e. pseudmonas
- Vibrio vulnificus (especially in patients with cirrhotic with sea water exposure!!!)
- Clostridium perfringens
- Candida spp
How about hypermucoid klebsiella? A single center study in Taiwan in 2012 found that klebsiella accounted for 17% of monomicrobial nec fas, with 2/3 of them being the hypermucoid variant. In Asian countries, HvKP necrotizing infection is as common as those caused by staph and strep.
In North America though? The first case report of community acquired HvKP associated was reported in 2015. See this article for details.
Hypermucoid variant Klebsiella (HvKP)
- Usually community acquired, highly virulence strain of KP that is typically pan-sensitive.
- Primarily in SE and E Asian countries but seeing this strain increasingly in the US.
- From a necrotizing soft tissue infection stand point, it has been reported in SE Asia beginning in 1996. Most info published in the literature are case reports,
- KP itself, in a single center study done in Taiwan 2012 found that KP in general accounted for 17% of monomicrobial nec fas, and 2/3 of these cases are HvKP. vs 22% staph vs 18% strep.
- Associated with higher mortality
- Main risk factors are baseline immunocompromised status, and 80% of pts with HvKP had DM
- Primary risk factor seems to be just diabetes! But this can affect completely healthy patients in the community.
- Pyogenic liver abscess
- Metastatic infection, likes to travel and stick to places.
- Associated infections
- Primary liver abscess, usually in the right lobe for some reason
- HvKP is the culprit organism in 9-12% in pts with primary liver abscesses
- Splenic abscess, SBP, PNA, soft tissue infection, osteo, UTI
- Associated endophthalmitis especially if bacteremic or presence of abscess in up to 50% of pts
- Not so much if pulmonary or urine
- String Test! > 5mm = diagnostic.
- Capsular subtypes: some are more virulent, K1, K2, rmpAvirulence-associated gene
- Fortunately, most are pan-sensitive
- Penicillin or cephalosporins = main stay, but if treating for a liver abscess, should cover for anaerobes as well.
- Surgical drainage if e/o abscess
- If concerned for metastatic infection, combination of surgical and medical therapy depending on location of the infection