Thanks to Kevin and Brayden for presenting a 36yo F with no medical history presenting with acute abdominal pain, nausea, and anorexia. Her AST/ALTs were in the thousands and she was ultimately diagnosed with acute hepatitis A! Incidentally her HB Core Ab came back “borderline…”
AST ALT Elevation
- 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!)
- Acute viral hepatitis (HAV, HBV, HCV, HEV, HSV, CMV, VZV, parvovirus)
- Less common:
- Autoimmune hepatitis
- Acute Budd Chiari
- Reactivation HBV, HDV
- HLH (we seem to see this a lot in this hospital for some reason?)
- Malignant infiltration
- Wilsonian Crisis (severe hemolysis and impending acute liver failure in setting of Wilson’s)
- For acute viral hepatitis, ALT is typically higher than AST.
- Global, 1.4 mil cases per year, can be sporadic or epidemic form
- Fecal oral route, either person-to-person contact or ingestion of contaminated food or water.
- Other risk factors: Sexual transmission (anal/oral sex), day care, consumption of raw or undercooked shellfish, veggies, or eating food prepared by an infected food handler.
- Incubation period: 15-50 days, average of 28 days.
- Acute onset N/V, fever, anorexia, abd pain are typical.
- Bilirubinuria, pale stools can also be seen within a few days.
- Jaundice + pruritus. Jaundice peaks within 2 weeks.
- Exam: Jaundice, hepatomegaly, RUQ pain.
- Serum aminotransferases often > 1000 IU/dL, bili typically < 10, alk phos can be nrl to mildly elevated. ALT is commonly higher than AST.
- Kids: Can be asymptomatic.
- Serum Anti-HAV IgM is diagnostic, detectable at time of symptom onset, remain detectable for 3-6 months after infection.
- Anti-HAV IgG: remain detectable for decades, protective vs future infections. Detection of anti-HAV IgM and IgG reflects past infection or vaccination.
- Primarily supportive, but transfer to a transplant center might be indicated if pt goes into fulminant liver failure (severe acute liver injury with encephalopathy and impaired synthetic function i.e. INR >5 in patients without pre-existing liver disease)
- Report to public health! Fax a confidential morbidity report over to Santa Clara County Department of Public Health
- Single Antigen inactivated virus: 2 IM doses 6-18 months apart
- Combo HAV and HBV inactivated virus vaccine: Adults only, 0, 1, 6 mo (3 doses total)
- Generally pretty good, less than 1% go into fulminant hepatic failure.
- Risk factors for severe complications: > 50, underlying liver dz
- Other Complications
- Relapsing hepatitis: Up to to 10% of pts experience a relapse of sx 6 months after the acute episode for ~ < 3 weeks. Multiple relapses can occur. These patients usually make a complete recovery
- Autoimmune hepatitis: HAV can trigger development of autoimmune hepatitis.
- Cholestatic hepatitis: Prolonged period of jaundice > 3 months, typically self-resolving
Hepatitis B serologies made ridiculously simple
Thanks Elan for presenting a case of a 91 year old F presenting with a progressively painful and erythematous rash, 2 weeks after she was treated with presumed Shingles by her PCP. It turned out that she had superimposed cellulitis over her healing Shingles lesions and possibly elements of post-herpetic neuralgia, requiring a Dilaudid PCA for pain control.
Lame joke of the day: Shingles + Cellulitis = Shinglelitis, get it?
- Risk inc with age, esp for pts > 50, but it can develop at any age
- Fortunately, most people will only have one outbreak in their life time, < 4% recurrence
- Reactivation of the varicella zoster virus in sensory ganglia after a long latency period following primary infection from varicella (chicken pox). When the virus activates, the virus travels down the nerve fibers to the skin, hence a dermatomal distribution.
- Weakening of the immune system is associated with outbreaks, i.e. AIDS, lymphoma, immune-suppressives.
- 2-3 days prior to rash: pt might develop a tingling sensation, hypersensitivity, or itching over a particular dermatome. Later on vesicles on an erythematous base develop. Painful and very sensitive.
- Blisters form over 3-5 days, then dry and crust over the next 5 days
- Blisters are CONTAGIOUS until the vesicles scab over.
- Keep affected area dry and clean!
- Expanding rash or blisters that persist for > 2 weeks indicate immune-compromised status
- Most common is post-herpetic neuralgia
- 10% of patients, inc with age
- Pain can be very debilitating, some patients need to be admitted for pain control.
- Zoster ophthalmicus
- Involves the eye, seen in 10-25% of cases when shingles hit V1
- Antiviral should be administered ASAP, preferably within 72 hours of onset of sx.
- Valacyclovir is recommended, 7-day course, 1000mg PO TID
- Alternative: Acyclovir 800mg PO 5 times daily x 7-10 days, Famciclovir 500mg PO TID.
- If e/o keratitis or uveitis, topical steroids can be used.
- Can lead to vision loss, especially with corneal scarring. Some patients would require corneal transplant.
- Post-herpetic neuralgia occurs in 36.6% of pts over 60, and 47.5% over age 70.
- Disseminated zoster
- If > 3 contiguous dermatomes or 2 separated dermatomes are affected.
- Bacterial infection of the skin:
- Risks inc with scratching
- Inc risk of scarring
- Ramsey Hunt Syndrome:
- Reactivation of VZV at the geniculate ganglion.
- Triad of Ipsilateral facial paralysis, ear pain, vesicles on face/ear or IN THE EAR. Can lead to deafness, tinnitis or vertigo due to vestibulocochlear nerve involvement.
- Mgx: Anti-viral within 72 hours, steroids. Hearing loss is likely permanent so treat ASAP.
- Primarily clinical
- Swabbing ulcer/vesicular fluid for HSV PCR has high sensitivity, quick turn around time.
- Acute management
- Anti-viral: Valacyclovir, famiciclovir, acyclovir. Start ASAP and preferably even before blisters occur. Effectiveness is greatest if antiviral is started within 72 hours of onset of symptoms (even before vesicles appear if clinical suspicion is high enough!)
- IV antiviral recommended for disseminated disease
- Options: Acyclovir (5 times a day dosing), Valacyclovir (TID dosing), famiciclovir (TID as well).
- Help shorten duration and complications
- Pain control:
- Lidocaine, capsaicin, gabapentin, Lyrica.
- Use opioids if and only if necessary.
- Antidepressants i.e. Cymbalta and Effexor have variable benefits for post-herpetic neuralgia.
- Keep area dry and clean, DO NOT SCRATCH.
- Infection Control:
- Localized herpes zoster: Standard precautions, contact
- Disseminated: airborne + contact
- Immunocompromised patient: airborne + contact regardless
- Previously received 2 doses of varicella vaccine: Monitor for 8-21 days for sx
- Previously only received 1 dose of varicella vaccine: Should get the 2nd dose ASAP (minimum of 4 weeks apart from 1st dose). Monitor for sx.
- No prior vaccination: Potentially contagious from days 8-21 post exposure, should be removed from patient care duties. Post-exposure vaccination should be provided ASAP. If varicella vaccination is contraindicated (i.e. pregnant), varicella-zoster immune globulin is recommended.
- Vaccinate children
- Vaccinate adults > 50 regardless of whether they have had chicken pox or shingles and regardless of whether they had the older vaccine
- Older: Weakened live virus, Zostavax
- Newer: Recombinant Herpes Zoster vaccine, Shingrix, 2 doses IM, 2-6 months apart, at least 2 months after the older vaccine. Contains inactivated parts of the virus, not a live vaccine.
- Effectiveness: 97% effective in preventing shingles for pts > 50, vs Zostavax which is 50-64% effective.
- Reduces post-herpetic neuralgia if you get it shingles
Gray Medicine had an interesting case of a 80yo F with history of treated TB (60 years ago), thoracic artery aneurysm s/p recent TEVAR, presenting with 3-4 months history of throbbing chest and back pain. She was admitted one month prior to the same complaint, CXR and CT Cx did not reveal significant pathology other than mild distal TEVAR graft dilatation. She presents 1 month later with worsening chronic chest pain, anorexia, weight loss.
This is the chest X-ray during this current hospitalization…
Burn this image into your head! This is a classic miliary pattern on a chest radiograph! The term miliary stems from millet seed, a term used to describe a group of small-seeded species of cereal crops or grains
Subsequent chest CT revealed innumerable bilateral pulmonary nodules, which were not present a month prior.
Let’s go through possible causes for a miliary pattern on a chest radiograph. In general it can be divided into three categories. The DDx can be quite wide!
In our case, given that our patient is an elderly woman with a remote history of treated TB, this presentation is highly concerning for miliary TB leading to reactivation. In general, miliary and disseminated TB are often used interchangeably. Disseminated TB refers to TB that affects at least two organ systems.
The most commonly affects organs are:
Our patient was placed on airborne, and ultimately her sputum was MTB PCR positive! She has TB!
Presentation of Miliary TB
- Very common: B-symptoms, FFT, typically subacute to chronic. 80-95% will have a fever.
- Miliary, unlike typical TB, can present with acute sepsis or respiratory failure.
- Pain/organ dysfunction based on location of the spread. Basically can affect anywhere. Hepatic TB, 79% of cases are due to miliary TB. Other commonly affected organs are spleen, adrenals, BM, lymphatics, and CNS.
- Other manifestations: DIC, hyponatremia, pan-cytopenia, 50% cases will have normocytic anemia.
- Immunocompromised status
- Extremes of age (infants, elderly)
- Post transplant
- Other medical co-morbidities (CKD, cirrhosis, EtOH, etc)
- Chest radiograph: Classic faint reticulonodular infiltrate uniformly throughout lungs.
- CT is more sensitive for miliary TB and usually is recommended. Typical finding might reveal numerous 2-3mm nodules but this is not specific.
- Tissue, fluid, or lymph node biopsy
- Gastric aspirate
- Ultimately combination of clinical diagnosis with support labs/imaging.
- Gold standard: AFB and culture + MTB PCR
- All patient should have mycobacterial blood cultures
- Urine mycobacterial cell wall glycolipid lipoarabinomannan (urine LAM) is a highly specific test with high sensitivity in HIV patients for disseminated TB.
- Intensive Phase: HREZ (aka RIPE) x 2 months
- R: Rifampin
- I: Isoniazid
- P: Pyrazinamide
- E: Ethambutol
- Continuation Phase
- After, 2 months of HREZ (RIPE), the continuation phase consists of 4 months of isoniazid and Rifampin.
- Choice of medication and duration will change depending on resistance of the organism and location affected
- Corticosteroids: Indicated if meninges or pericardium is involved.
- Make sure to fill out a GOTCH form (not the GOAT form, as someone answered on Kahoot this morning) for Santa Clara County if you have a patient with active TB since a safe dispo will involve multiple disciplines and careful planning!
Thanks to Amran for presenting an interesting case of a 84yo M with RA on MTX & Prednisone, and an unspecified self-resolving total body rash 1 month prior to presentation, presenting with pain, redness, and vision in both eyes. Detailed fundoscopic exam was consistent with bilateral anterior granulomatous uveitis as well as retinitis, consistent with a panuveitis picture. Initial work up revealed RPR and EIA positivity, his HLA-B27 also returned positive but he has no other findings suggestive of spondylosing arthropathy. His vitreal centesis returned positive for VZV!
- Tertiary syphilis without CNS/ocular involvement
- Panuveitis secondary to VZV
- Incidental HLA-B27 without e/o ankylosing spondylitis
Let’s start off with a basic review of the eye anatomy:
The Uvea consists of the iris, ciliary body, and the choroid. Uveitis is inflammation of any of these structures.
The Standardization of Uveitis Nomenclature (SUN) Working group guidance on uveitis terminology categorizes uveitis anatomically as follows;
- Anterior uveitis; localized primarily to the anterior segment of the eye, involving iris and pars plicata.
- Intermediate uveitis; localized to the vitreous cavity and pars plana, presence of WBC in the vitreous.
- Posterior uveitis; localized to the choroid and retina.
- Panuveitis; inflammation involving anterior, intermediate and posterior uveal structure
Uveitis can be further classified into granulomatous (presence of macrophages, multinucleated giant cells) vs non-granulomatous. A granulomatous uveitis is typically more likely to be an infectious process (although can still be idiopathic or Sarcoidosis).
Etiology of Uveitis
- Usually unilateral, might have other clues such as presence of vesicles.
- Ocular toxoplasmosis for some reasons occurs more frequently in immunocompetent hosts.
- Lyme Disease
- Accounts for less than 1% of cases of uveitis but can affect any part of the eye.
- TB (Yes ocular TB exists!)
- Uncommon in North America, suspect in endemic regions and worsening sx with glucocorticoids.
- Almost exclusively in immunocompromised hosts i.e. AIDS patients.
- CD4 < 50 typically.
- Bartonella (ocular bartonellosis) aka Cat Scratch Disease:
- Typically unilateral, has a characteristic “macular star” on fundoscopic exam.
- West Nile virus
- Ebola (case reports)
- Zika virus
- Varicella Zoster Virus: Can affect any part of the eye
- Non-infectious: Most common = HLA-B27 related arthropathies and reactive arthritis, tends to be unilateral and causes an anterior uveitis picture
- Ankylosing spondylitis
- Relapsing polychrondritis:
- Juvenile idiopathic arthritis
- Psoriatic arthritis
- Reactive arthritis
- TINU (tubulointerstitial nephritis and uveitis) syndrome
- Uncommon, occurs in adolescent/young F, fever, myalgias, anemia, LFT elevation, chronic uveitis, interstitial nephritis.
- MS: Optic neuritis
- Japanese and Hispanics, bilateral panuveitis, neurological/auditory sx
- Penetrating trauma
- Rifbutin, fluoroquinolone, monoclonal ab
- Other conditions that might mimic uveitis
- Retinal tears
- Ocular melanoma
- Pigmentary dispersion syndrome
- Retinitis pigmentosa
- Treat underlying cause
- If viral: Anti-virals (acyclovir, valacyclovir), add on topical corticosteroids.
- Non-infectious uveitis: Management typically with topical steroids. If posterior, some have suggested using difluprednate or periocular glucocorticoid injections. Systemic tx is reserve for pts with bilateral disease, inability to tolerate intraocular injections, or systemic conditions i.e. Behcets.
- If refractory to steroids in non-infectious causes, can consider MTX, azathioprine, mycophenolate, cyclosporine, or tacrolimus.
- TNF alpha inhibitors u.e. adalimumab has good evidence in the tx of non-infectious intermediate, posterior, and panuveitis. Can also be considered first line in management of Behcet.
- Sulfasalazine has been shown in a few small studies to prevent HLA-B27 associated uveitis.
Please refer to this previous blog post for more details on tertiary syphilis!
Today, we discussed the case of a Vietnamese man who presented with chronic cough, 40 pound weight loss, and joint pain, found to have cavitary lesions in his lungs with work up revealing pulmonary TB as well as tophaceous gout on urate-lowering therapy with allopurinol leading to SJS/TEN.
- Cavitary lung lesions have a broad differential (see below) aside from TB.
- Risk factors for developing SJS/TEN include HIV (100x higher risk), genetics (especially Asians and South Asians), autoimmune diseases, malignancy, and high dose/rapid infusion of offending meds. Consider genetic testing prior to starting meds associated with this allergy (allopurinol, sulfa drugs, PCNs, AEDs, etc.) in at risk populations.
- Nikolsky sign can be positive in SJS/TEN, staph scalded skin syndrome, and pemphigus vulgaris
- Time of onset is 1-3 after starting the offending drug
- SCORTEN score is useful for determining prognosis
- Early use of cyclosporine in patients with SJS/TEN has shown significant reduction in mortality.
DDx for cavitary lung lesions
- Pyogenic (necrotizing pneumonia, septic emboli, lung abscess)
- Atypical (MTB, fungi)
- Liquid (lymphoma, KS, lymphomatoid granulomatosis)
- Solid (squamous, GU>GI)
- Foreign body granulomatosis
SJS/TEN (Steven Johnson vs toxic epidermal necrolysis)
- < 10% = SJS, > 30% = TEN, in between = Overlap
- Common causes
- Sulfa drugs
- Abx (PCN, quinolones)
- Infx: Mycoplasma, graft-vs-host
- Risk factors
- HIV (100x higher risk)
- There are a lot of them (check on uptodate for specific drugs) but a couple examples are:
- HLA-B*58:01 (allopurinol)
- Patients with this positive gene has higher risk for severe cutaneous hypersensitivity reaction to allopurinol including SJS and TEN. High risk Asian populations carrying this gene are Korean, Thai and Han Chinese.
- HLA-B*15:02 is recommended before starting carbamazepine in Asians and South Asians
- Cytochrome CYP2C19 polymorphism
- Autoimmune disease
- High doses and rapid infusion of medications
- Clinical Presentation
- 1-3 weeks after offending drug
- Fever >39
- Influenza-like symptoms (malaise, myalgias, arthralgias) x 1-3 days
- Conjunctival itching or burning
- Cutaneous findings:
- Acute onset macules over face, trunk, may form flaccid bullae
- Nikolsky sign:
- Positive when shear stress on the skin i.e. rubbing results in exfoliation. Indicates a pathology at the dermal/epidermal junction.
- Positive in
- Staphylococcal scalded skin syndrome
- Pemphigus vulgaris
- Asboe-Hansen sign (AKA bullae spread sign)
- Mucous membrane involvement.
- Eyes, mouth lesions
- Respiratory sx
- SCORTEN score
- Mortality with SJS is 10%, TEN 30%
- Supportive care for skin
- Pain control
- IV fluids
- Prevention of vulvovaginal sequelae
- Ocular management
- Evaluate for loss of surface epithelium
- Opthalmic therapy
- Saline rinses to remove debris
- Artificial tears
- Topical steroids
- If extensive sloughing, then amniotic membrane transplantation (prokera ring)
- Adjunctive therapies
- Steroids: may lead to higher rates of complications
- IVIG: conflicting data
- Cyclosporine: one large case series from Spain and two systematic reviews have shown that cyclosporine given at 3 to 5 mg/kg may slow the progression. Inhibits T cell activation and thus prevents the production and release by cytotoxic T cell and natural killer cells of cytokines that could propagate SJS/TEN.
- A study on 71 patients of whom 49 were treated with cyclosporine and 22 with other therapies found mortality rates were 10% and 32% respectively. Expected mortality based on SCORTEN for the cyclosporine group was 24% and 29% in the other group.
- A 2018 meta-analysis on 255 patients with TEN found that treatment with cyclosporine was associated with a 70% reduction in mortality risk
Bonus info on gout:
- Acute flare:
- Colchicine (avoid in severe renal or hepatic impairment or with meds that inhibit CYP450 system)
- Indications for urate-lowering therapy for chronic treatment
- Frequent or disabling gout flares
- Clinical or radiographic signs of joint damage
- Tophaceous deposits in soft tissues or subchondral bone
- Gout with renal insufficiency (CrCl<60)
- Recurrent uric acid nephrolithiasis
- Urinary acid excretion >1100 mg/day)
- Goal uric acid is <6mg/dL
- Agents for chronic management
- Xanthine oxidase inhibitors
- Allopurinol, lower dose for CKD3 or higher renal disease
- Febuxostat, very expensive, cardiovascular and hepatic side effects
- Uricosuric drugs: ineffective if CrCl<50. Can worsen kidney injury. Avoid use if GFR <30
- Pegloticase, fast improvement of symptoms, contraindicated in G6PD deficiency
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
Sorry for posting this late!
A 38yo M with history of asthma, but otherwise healthy, presents acute onset seizure as well as LLE, LUE weakness and paresthesia. He has never had seizures before prior to this. History revealed that patient was born in Honduras, and he grew up on a pig farm, and his brother actually had a history of Taeniasis. MRI revealed a cystic structure with a thin septae/soft tissue component within, consistent with neurocysticercosis!
Let’s talk about seizures for a little bit.
In developeED countries, the most common cause of epileptic seizure is often idiopathic.
In developING countries, the most common cause of epileptic seizure in both kids and adults, is neurocysticercosis (NCC).
Neurocysticercosis: When larvae form of the Taenia solium (aka the tapeworm) move to non-GI tissues and into CNS.
Presentation: Viable (asx, many years) -> degenerating (loses ability to evade immune system, localized inflammation) -> non-viable (calcified granulomas, can still cause szx)
- Most common form of neurocysticercosis, > 60% of cases
- 3-5 years after infection but can occur > 30 years after initial exposure.
- Seizure = most common manifestation. Occur in setting of cysts degeneration or granulomas.
- Endemic areas: NCC is the most common cause of adult onset seizure
- Headaches, usually mild
- Rare complications: vision, focal neuro, meningitis, encephalitis (higher parasitic load)
- Most, however, are asx and diagnosed incidentally.
- When NCC occurs in the spine, eyes, ventricles, subarachnoid space. More commonly in adults.
- Can cause increased ICH, hydrocephalous
- Sub-arachnoid form is most severe, esp in the basilar cisterns. 5% of cases.
- Spinal: 1% of cases, can cause localized/dermatomal pain.
- Ocular: 1-3% of cases, impaired vision, eye pain, diplopia, chlorioretinitis, retinal detachment.
- Extra Neural
- Most common: muscles, subcutaneous
- Cardiac has been described…
- Stool O&P can help
- Eosinophilia is uncommon
- Imaging: Clinical history, endemic history, enhancing cystic lesion on MRI is very likely.
- CT: Useful for IDing calcifications, parenchymal cysticerci, and eye involvement
- MRI: Useful for small lesions, degenerative changes, edema, and visualizing scolices within calcified lesion
(Mahale et al. Extraparenchymal (Racemose) Neurocysticercosis and Its Multitude Manifestations: A Comprehensive Review. J Clin Neurol. 2015 Jul;11(3):203-211)
- Serology: Should be performed for confirmation Enzyme Linked Immunoelectrotransfer Blot Ab is highly sensitive and specific, but takes time and availability is limited.
- Latest IDSA Recommendation in 2018
- Calcified lesions: symptomatic management only with anti-epileptics
- Enhancing lesions
- Patients who acquired NCC in a non-endemic area should have their household members screened.
- Screen for latent TB, strongyloides infection given possibility of prolonged steroid use
- Fundoscopic exam is recommended for all patients with NCC
- Prior to anti-parasitic therapy, all patients should be treated with corticosteroids prior to initiation.
- Anti-epileptics should be used in all patients with seizures.
- Albendazole + praziquantel is better than monotherapy with albendazole if greater than 2 lesions. 1-2 lesions, monotherapy with albendazole should suffice.
- Intraventricular neurocysticercosis
- Minimally invasive surgical removal prior to antiparasitic therapy to minimize inflammatory response.
- Subarachnoid neurocysticercosis in the basilar cisterns or Sylvian fissures
- Prolong course of anti-parasitic until radiologic resolution, can last more than a year.
- Corticosteroids recommended while on treatment but methotrexate can be considered a steroid-sparing agent in patients requiring prolonged anti-inflammatory.
- Surgery case by case
- Spinal neurocysticercosis
- Combination surgery and anti-parasitics, start steroids first with evidence of spinal cord dysfunction and prior to antiparasitics
- Surgery preferred over medical management.
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
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