We discussed a case about a young woman with hx of STIs (syphilis and chlamydia s/p treatment), subacute hx of migratory polyarthralgias, who presented with fevers and acute arthritis / tenosynovitis of her left index finger + thumb. She was found to have gram negative diplococci bacteremia and diagnosed with disseminated gonorrhea.
Framework for arthritis
Categorize differentials based on non-inflammatory vs inflammatory, as well as mono- / oligo- / polyarticular.
CDC screening recommendations
Men: those at high risk (MSM)
Women: can be asymptomatic -> complications of STIs (eg PID, infertility)
We discussed a young male with past medical history of syphilis (incompletely treated) and recently diagnosed HIV (4 days prior to admission) who was admitted for elevated liver enzymes found incidentally. Liver enzymes consisted of mildly elevated alkaline phosphatase and bilirubin but extremely elevated AST/ALT in 4000s. Only a few entities cause elevation to the thousands. He was found to have acute co-infection of HIV and Hepatitis B.
If AST/ALTs are in the thousands, there are only a few entities that can cause this:
Ischemia (shock liver)
Toxins (Tylenol is most common), Amanita aka magic mushrooms, herbal supplements (we don’t know what they put in these!)
HLH (we seem to see this a lot in this hospital for some reason?)
Wilsonian Crisis (severe hemolysis and impending acute liver failure in setting of Wilson’s)
According to the CDC, approx 10% of people with HIV in the US also have chronic or acute HBV. There is accelerated progression to liver disease and increased all cause mortality for HIV-HBV co-infection when compared to HIV mono infection. Monotherapy of HBV is not recommended in the HIV co-infected due to the evolution of HIV resistance. Recommended antiretroviral regimens for treating persons with HIV-HBV coinfection should include three medications that are active against HIV and two medications that are active against HBV.The preferred regimens include tenofovir alafenamide-emtricitabine, tenofovir DF-emtricitabine, or tenofovir DF plus lamivudine as part of a fully suppressive antiretroviral regimen.
We discussed a case of a young man who presented to the hospital after having a seizure. He had a history of neurocysticercosis complicated by seizures many years ago. His most recent seizure was in the setting of restarting albendazole.
We discussed how to come up with a broad and organized ddx for the cause of seizures using the MIST mnemonic, practical knowledge for acute seizure management, and highlights regarding the management and treatment of neurocysticercosis.
Acute seizure management
Check the patient’s ABCs and IV access
Check for hypoglycemia
Ativan 2-4 mg IV pushes x3
continuous seizure that lasts ≥5 min OR
≥2 discrete seizures w/out return to neuro baseline between seizures
Neuroimaging can definitely diagnose neurocysticercosis
Serologies can be helpful. The test of choice is enzyme-linked immunoelectrotransfer blot (EITB)
Antiparasitic therapy can cause degeneration of cysticerci -> inflammatory response.
In patients with ocular disease, the inflammatory response can cause edema and lead to blindness. Therefore, always consult ophthalmology to rule out ocular neurocysticercosis prior to starting antiparasitics.
In patients with CNS disease, the inflammatory response can cause edema and lead to seizures. Therefore, concomitant corticosteroids with antiparasitic medications (and AEDs) is recommended.
Bronchiectasis, sinusitis and obstructive azoospermia who have no evidence of cystic fibrosis
Primary Ciliary Dysfunction
Allergic bronchopulmonary aspergillosis
should be suspected in patients with a long history of asthma that is resistant to bronchodilator therapy and associated with a cough often productive of sputum that is mucopurulent or contains mucous plugs.
Thanks to Dr. Szumowski for sending us the case of a middle aged man who presented with acute L knee swelling and pain one week after a viral URI syndrome, initially concerning for septic joint. His clinical course was complicated by recurrent high daily fevers, a diffuse maculopapular rash, and knee arthrocenteses and joint washes that were clean leading to a diagnosis of Still’s disease!
Still’s disease is a diagnosis of exclusion! Yamaguchi criteria can help with ruling in the diagnosis.
Still’s remains a multi-systemic disorder of unknown etiology because it’s difficult to diagnose and rare (0.16 cases per 100,000).
RF and ANA are generally negative but can be positive in <10% of patients with Still’s in low titers.
~66% of patients present with sore throat secondary to cricothyroid perichondritis or aseptic nonexudative pharyngitis.
The disease is often recurrent. Predictors of poor outcome include erosive polyarthritis on presentation and shoulder/hip involvement.
Described in 1897 by George Still, it is a systemic inflammatory disorder of unknown etiology
Some clarifications on nomenclature:
Systemic juvenile idiopathic arthritis (sJIA): first presentation <17 years old, previously referred to as Still’s disease
Adult onset Still’s disease (AOSD): first presentation > 17 years old
Epidemiology of AOSD:
0.16 cases per 100,000
No sex predominance (F=M)
Bimodal age distribution with peak between 15-25 and another 36-46 years of age. New diagnosis in patients >60 have been reported.
Poorly understood but likely a combination of genetic predisposition, environmental triggers (viruses such as echo, coxsackievirus B4, mycoplasma, yernisnia, lyme, etc), activated innate immunity leading aberrant production of pro-inflammatory cytokines
High ESR and CRP
Very high ferritin levels
Ultimately a clinical diagnosis so it’s important to exclude potential mimickers
Yamaguchi criteria are the most sensitivity (93.5%)
Fautrel’s Criteria are the most specific (98.5%)
Largely empirical since clinical trial data is lacking
High dose steroids are first line when systemic symptoms predominate
MTX is second line
NSAIDs are not good
Biologic agents for refractory cases (IL1 antagonist anakinra or canakinumab), IL6 antagonist tocilizumab, or TNF inhibitors.
Monocyclic pattern (systemic single episode)
Polycyclic pattern (multiple episodes, usually <1 /year)
Chronic pattern (persistently active disease with poly arthritis)
Thanks to the Human Dx Project for providing us with this fascinating case of a middle aged woman with history of asthma who presented with acute onset of fever and epigastric abdominal pain as well as a chronic progressive cough, found to be febrile, tachycardic, and ill appearing, with E coli bacteremia of unknown source. Further history taking revealed a similar hospitalization several months prior with idiopathic E coli bacteremia. Strongyloides titers were sent and markedly elevated. She was treated with ceftriaxone and ivermectin and made a full recovery.
Absence of eosinophilia does not rule out strongyloides. Keep in mind that those presenting with severe illness and hemodynamic instability are commonly in a high cortisol state which can lead to eosinophil apoptosis. Also, in those with history of steroid use (even for short periods of time), eosinophil count can be negative.
Think of strongy in anyone with the right travel history, older age, malnutrition, HIV, or steroid use.
Signs and symptoms can be quite non-specific so a high index of suspicion is required to make the diagnosis.
Think of strongyloides in a patient with history of recurrent GNR bacteremia of unknown etiology!
Higher incidence noted going from yellow to orange to red on the map above
Typically in travelers to endemic areas, immigrants from endemic regions, or anyone with barefoot contact with infested soil.
Risk factors include older age, malnutrition, HIV, and steroid use
Signs and symptoms
Infected people can be asymptomatic or minimally symptomatic for years:
Could also have mild waxing and waning GI, skin, or pulmonary symptoms for years
Eosinophilia without symptoms
Skin: urticarial, larvae currens (see picture below), angioedema, erythroderma
Pulmonary: chronic cough, hemoptysis, recurrent pneumonia, astham that gets worse with steroids
Credit goes to Dr. Scott Burns from Roper Hospital in Charleston for his case on the Human Diagnosis Project.
Today we discussed a case of a young man with otherwise no medical history presenting with subacute dry cough, malaise, and weight loss. On exam he was septic on presentation with notable oral thrush. CXR revealed bilateral interstitial infiltrates and a RUL cavity with air fluid level which was confirmed on CT. LDH was elevated. He was confirmed HIV positive with a low CD4 count in the single digits, and BAL confirmed the diagnosis of PCP/PJP pneumonia!
Oral Thrush: NEVER assume normal, extremely rare in immunocompetent patients, so if you see this, consider whether the patient could be immunocompromised.
Cavitary Lung Lesion DDX
Bacterial: Legionella, rhodococcus
Fungi: PCP/PJP, mucormycosis, blasto
HIV with CD4 < 200
BMT, organ transplant patients
Rarely occurs in immunocompetent patients
Typically subacute onset of pulmonary symptoms, non-productive cough, fever chills, malaise, SOB
Might have other clues of immunocompromised status
CXR: Classic description is bilateral interstitial infiltrates
We recently had a case of a middle age man with SLE on chronic prednisone, ESRD on PD, presenting with acute on chronic shoulder pain x 10 days. Presentation was initially concerning for septic arthritis, and joint washout revealed gross purulence from the shoulder joint. Cultures were sent but no additional fluid studies were obtained.
A subsequent TTE, and later a TEE, confirmed a mitral valve vegetation concerning for concurrent infective endocarditis. However, multiple sets of blood cultures, fungal cultures, synovial fluid culture from the initial I&D/wash out, and even 16S PCR of the synovial fluid were all negative. This is a rare case of culture negative endocarditis which is later thought to be more likely Libman Sacs!
Risk factors: Advanced age, pre-existing joint dz, recent surgery or injection, SSTI, IVD, indwelling catheter, immunosuppression.
Most cases arise from hematogenous seeding, hence bacteremia is common.
Direct inoculation: usually due to trauma, surgery/injections, or wounds.
Usually mono-microbial, and Staph aureus is the most common cause of septic arthritis in adults.
GNR can be seen in older adults or in immunocompromised patients
Monoarthritis is most common
Edematous, painful, warmth, limited ROM
Older patients may not be febrile
20% of cases can present as oligoarticular or polyarticular infection. Polyarticular septic arthritis is more likely to occur in pts with RA
Most common affected joint is the knee
Could be a manifestation of infective endocarditis, esp amongst IVDU
Synovial fluid analysis and culture, should be obtained prior to abx
Positive gram stain or culture is gold standard and diagnostic
PCR only required in rare cases since most non-gonococcal cultures obtained prior to antibiotics return positive. Negative cultures can result due to recent abx or atypical organism.
In pts with purulent synovial fluid (WBC 50k-150k) but culture negative, a presumptive dx can be made.
Likelihood of septic arthritis inc with inc leukocyte count
Blood cultures should be obtained
Should also evaluate for endocarditis given most common organism is staph aureus
Always get a radiograph to evaluate for concurrent bone/joint involvement
CT/MRI can be useful if looking for an effusion
Viral (usually polyarticular), i.e. Zika, Dengue, chikungunya, parvo, rubella, adenovirus
Joint drainage, severe infectious may require repeated aspiration or even wash out.
Most cases are staph, MRSA cases on the rise
Suspect pseudomonas if pt is immunocompromised or has h/o IVDU
Intra-articular abx: typically not used
Staph aureus with bacteremia: At least 4 weeks
Staph aureus without bacteremia: at least 14 days IV, followed by 1-2 weeks PO
Bone involvement: 4-6 weeks
Any organisms, any bone involvement: 4-6 weeks
Other organisms: Typically at least 4 weeks
Culture Negative Endocarditis
Definition: Endocarditis without an identified organism in at least 3 independent blood cultures with negative growth after 5 days
2-7% of IE cases
3 most common causes:
Atypical organisms (fastidious bacteria i.e. zoonotic microbes, fungal)
Thanks to Dr. Olivia Lee for letting us know of the case of this middle-aged woman with h/o endometrial cancer s/p TAH/BSO who was BIBA on a 5150 for GD after being found living in her yard. Her medical clearance work up led to the diagnosis of endocarditis with a large abscess on the mitral valve leading to septic emboli to the brain, spleen, and kidneys as well as vitritis and endophthalmitis. She was also noted to have an indwelling mediport with a vegetation at its tip, showering emboli into her lungs. She successfully underwent urgent surgical replacement of her infected/destroyed valve.
Use Duke’s criteria to help with your pre-test probability of endocarditis. If patient meets criteria for definite endocarditis, consider going straight to a TEE.
TTE is not sensitive but highly specific for endocarditis. However, in a patient with concerning clinical features (see next bullet point), a TEE is necessary to evaluate valve condition and plan for surgical intervention. TTE is more useful if pre-test probability of endocarditis is low.
Indications for surgery
Valve dysfunction causing heart failure
Perivalvular extension with development of abscess, fistula, and/or heart block
Fungi or other highly resistant organisms that are difficult to treat with abx alone
Persistent bacteremia despite maximal treatment
Recurrent embolization with persistent vegetations
Large vegetations (>1 cm) with severe valvular regurg
S aureus prosthetic valve endocarditis
Indications for earlysurgery:
Prevention of embolic events
Most common cause of death in endocarditis is heart failure.
For a thorough review of endocarditis, please see our previous blog post here.
Some key learning points from our M&M case discussion today:
Ertapenem is a slow acting antibiotic and not an ideal empiric treatment in a patient who presents with sepsis or is acutely ill. So if you want to use a carbapenem for empiric coverage, pick meropenem or imipenem instead.
Fun fact: ertapenem is actually more expensive than mero/imi. The only use for ertapenem is in transitioning patients from hospitalization to home where its daily dosing is more favorable than the TID dosing of meropenem.
For diabetic foot ulcers, please refer to our SCVMC algorithm to help you figure out empiric antibiotics. Simply open the HHSConnect browser and type in diabetic foot in the search bar to pull up the algorithm.
If blood cultures take a longer time to speciate (in our patient, over 5 days), expect anaerobes because anaerobes are difficult to culture and are sent out for speciation. E coli is an organism that should speciate quickly and would grow in aerobic and anaerobic bottles. If a species is only growing in anaerobic bottles, then it’s probably not E coli.
Levofloxacin is the only fluoroquinolone that has a role in outpatient treatment of GNR bacteremia, other fluoroquinolones (like cipro) are less effective.
Avoid using fluoroquinolones for empiric treatment of E coli bacteremia or pyelonephritis because our VMC antibiogram shows ~25% resistance with fluoroquinolones.