A 42yo homeless man with AIDS not on ART with CD4 < 10, VL 440K+, presents with an acutely enlarging right-sided neck mass that was tender and firm, with associated fevers and malaise… Blood CrAg returned positive, and biopsy revealed encapsulated yeast with narrow based buds…
Yep, you’ve guessed it, it’s crypto!
Invasive fungal species, primarily C neoformans and C. gattii are seen, found world wide in soil. Associated with infections in immunocompromised hosts.
AIDS (AIDS defining illness)
Long term steroids
Solid organ transplantation
Most of the population have been exposed to the spores of C. neoformans, and in immunocompetent patients, most cases are asymptomatic to mild symptoms.
Typically inhaled and affects the lungs first, and then can disseminate to CNS (most feared), skin, solid organs, bones, etc
CNS: Feared, no-specific sx of fever, AMS, headache.
Disseminated disease requires at least 2 non-contiguous sites
Culture is definitive
GS: Encapsulated budding yeasts with narrow based buds on India Ink = characteristic
IF e/o dissemination, get CXR, urine, LP, blood cultures
Cryptococcal capsular antigen (CSF or blood) are > 90% sensitive and specific.
Cr titers correlate with organism burden and prognosis, but not helpful to follow during treatment and doesn’t correlate with tx response. Titers > 1:512 is associated with poor prognosis.
CSF or blood CrAg is diagnostic
Mild to moderate in immunocompetent hosts: Fluconazole for 6-12 months.
Alternatives are itraconazole, voriconazole, or posaconazole.
Immunocompromised hosts with mild-moderate pulmonary disease in the absence of diffused pulm infiltrates, CNS, or disseminated infection, can use fluconazole 6mg/kg (typically 400mg) daily for 6-12 months, with similar alternatives if fluconazole is not available/tolerated.
Immunocompromised hosts with severe disease or CNS infection: ARDS occur frequent in IC patients with cryptococcal pneumonia.
Induction: Ampho B + flucyotosine for minimum of 2 weeks.
Consolidation: Fluconazole 200-400mg daily x 8 weeks
Maintenance therapy is continued for at least 1 year.
Intracranial pressure control: Cryptococcal meningoencephalitis patients might need daily LPs to relief ICP, might require VP shunt. Do not use mannitol or acetazolamide.
Steroids not shown to be helpful.
ART: Usually not started with induction therapy due to a risk of IRIS.
ART is usually started 2-10 weeks after antifungal therapy has been started to minimize risk.
Today, we talked about the case of a middle-aged man from the Philippines who presented with a one year progressive pruritic rash involving the face, arms, and legs as well as a distal symmetric peripheral neuropathy, found to have lepromatous leprosy on skin biopsy!
Mycobacterium leprae and lepromatosis like to grow in cooler areas, so infection often manifests in the skin and the peripheral nerves.
Transmission is likely via respiratory route, through broken skin, and by touching armadillos!
Early recognition and treatment is important to prevent injury to peripheral nerves.
DDx for rash + neuropathy
Lyme (usually cranial nerves, radiculopathy)
Zoster (tends to be painful rather than pruritic and localized to a dermatome)
WNV (flaccid paralysis)
Our patient presented with a pruritic rash and largely a distal symmetric peripheral neuropathy. We generated the following Venn diagram in report to help us with the diagnosis:
AKA Hansen’s disease
Infection caused by mycobacterium leprae and mycobacterium lepromatosis, separate species that cause similar clinical disease. They are both obligate intracellular parasites.
Involves the skin and peripheral nerves
Early treatment is important to prevent involvement of the eyes, hands, and feet due to neuropathy. The neuropathy is often non-reversible.
205 new cases detected in the US in 2010. 75% among immigrants (most commonly India, Brazil, Indonesia, Bangladesh, and Nigeria)
Unknown but probably respiratory route especially in lepromatous leprosy. Sometimes can transmit through broken skin. Also from armadillos.
Most people do NOT develop disease after exposure. Risk factor for disease development include older age, genetic influences, and immunosuppression.
Grows in cooler areas
Described in categories pertaining to how much bacillary burden of disease is present with tuberculoid being the least amount and lepromatous having the highest disease burden.
Hypopigmented or reddish patches on the skin
Typically involve the earlobes with nodular thickening and distributed symmetrically on the body in lepromatous leprosy.
Diminished sensation or loss of sensation within skin patches
Paresthesias of hands/feet
Neuropathy occurs early in disease course
Painless wounds or burns on the hands or feet
Lumps or swelling on the earlobes or face
Tender, enlarged peripheral nerves
Late findings in disease course:
Weakness of the hands with claw fingers, foot drop, facial paralysis, lagophthalmos (can’t close eyes completely due to CN7 palsy), lack of eyebrows/eyelashes, collapsed nose, perforated nasal septum.
Intermittent bacteremia can lead to focal lesions in various organs (liver, bone marrow, testicles and larynx)
Consider it in patients with skin lesions and/or enlarged nerve(s) accompanied by sensory loss.
No reliable blood or skin tests available.
Usually clinical and skin biopsy
Goal: Prevent and/or minimize injury to peripheral nerves!
Often times it’s loss of sensation but later can progress to painful neuropathy
Dapsone plus rifampin for tuberculoid leprosy. Clofazimine is added for lepromatous leprosy.
Duration can be up to 24 months
Treat neuritis with steroids for a prolonged course
Make sure to screen for G6PD deficiency before prescribing dapsone
Monitor liver function with rifampin
Clofazimine (causes phototoxicity) is not available in US pharmacies and must be obtained from the NHDP.
May take a few years for skin lesions to resolve completely with treatment
Very curable, low relapse rates, typically no drug resistance
We worked through a case from the Human Diagnosis Project with a 57 yo M originally form Guatemala (moved to US 25 years ago) with a history of pre-DM and recently diagnosed and treated Lyme disease presenting with 2 months of persistent fever, chills, malaise, and myalgias. He received extensive work up, and everything turned (including TEE, LP, SPEP, rheum, BM biopsy, HIV) were negative. He had splenomegaly on exam, and CT CAP revealed hilar LAD + LLL tree-in-bud along iwth a 20cm spleen. The patient was ultimately diagnosed with DLBCL, AND cryptococcal pneumonia secondary to immunosuppression from his lymphoma!
Credit: Dr. Ron Cho, New York Medical College, Internal Medicine.
Fever of Unknown Origin
Fever > 38.3 °C on multiple occasions
Duration > 3 weeks
Uncertain diagnosis after 3 outpatient visits or 3 days in the hospital (revised, used to be 1 week inpatient investigation) or 1 week of “intelligent and invasive” ambulatory investigation
TB is the single most common infection in most FUO series, can be extrapulmonary, military, or pulmonary. May occur concurrent in AIDS patient, leading to a more subtle presentation.
Bacterial endocarditis (2-5% of these are culture negative bacterial endocarditis, i.e. from Coxiella brunetii and tropheryma whipplei).
Super rare causes of endocarditis with difficult to grow culture: Mycoplasma, Legionella, Bartonella, Brucella, HACEK organisms
TEE is positive in > 90% of cases of FUO from infective endocarditis.
Viral i.e. EBV
Malignancy: Most common are lymphoma and leukemia.
Systemic Rheumatic disease
Adult onset Still’s disease: young and middle age adults, daily fevers, arthritis, evanescent rash.
Factitious fever: Psych, predominantly affects F and healthcare professionals
Disordered heat homeostasis after a stroke or from hyperthyroidism
Multiple concurrent infections
Hereditary periodic fever syndromes
Unidentified: 19% of cases are unidentified.
Get a detailed history, including fever pattern exposure history, sexual history, family history, medications.
Do not start empiric therapy unless pt is neutropenic or unstable, or you have a high-suspicions for GCA or culture negative endocarditis.
Most common type of NH Lymphoma, representing 25% of cases
Median age: 64, 55% men. Also accounts for 25% of childhood NHL.
Caucasians at higher risk and esp patients of Swedish and Danish ancestry
Other risk factors: HIV, h/o radiation or chemotherapy
Heterogenous group of tumors that arise from mature B cells in (90% of cases, the other 10% from T cells)
Most common mutations found in DLBCL:
BCL6 gene mutation
Nodal and extra-nodal manifestation at time of diagnosis. Most common extra-nodal manifestation is bonemarrow or GI tract.
Typically pts present with a mass, most commonly in the neck, abd, or mediastinum but it can manifest anywhere.
Painless LAD might be present in 2/3 of cases.
Less than 50% will have B-sx.
Can present with pancytopenia. Might see elevated LDH, uric acid, and calcium.
Excision LN or tissue biopsy, excisional LN is preferred
Ann Arbor Criteria
Stage I – disease in single lymph node or lymph node region.
Stage II – disease in two or more lymph node regions on same side of diaphragm. Note: Stage II contiguous means two or more lymph nodes in close proximity (side by side).
Stage III – disease in lymph node regions on both sides of the diaphragm are affected.
Stage IV – disease is wide spread, including multiple involvement at one or more extranodal (beyond the lymph node) sites, such as the bone marrow (which is involved commonly), liver, pleura (thin lining of the lungs).
Spleen is considered nodal
1st line is RCHOP (3 cycles) and local regional radiation, 6-8 cycles of R-CHOP is an acceptable alternative.
Emerging data, DA-EPOCH is better for younger patients < 60 yo and with certain phenotypes
Double Hit Lymphoma: Lymphoma resembling DLBCL but has MYC gene translocation AND rearrangement of BCL 2 or BCL 6. RCHOP still first line but overall prognosis is worse. DA-EPOCH-R might work better.
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!)
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)
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
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.
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.
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.
Swabbing ulcer/vesicular fluid for HSV PCR has high sensitivity, quick turn around time.
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
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.
Localized herpes zoster: Standard precautions, contact
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 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.
Extremes of age (infants, elderly)
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
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
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 aGOTCH 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.
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.
Japanese and Hispanics, bilateral panuveitis, neurological/auditory sx
Rifbutin, fluoroquinolone, monoclonal ab
Other conditions that might mimic uveitis
Pigmentary dispersion syndrome
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.
SJS/TEN (Steven Johnson vs toxic epidermal necrolysis)
< 10% = SJS, > 30% = TEN, in between = Overlap
Abx (PCN, quinolones)
Infx: Mycoplasma, graft-vs-host
HIV (100x higher risk)
There are a lot of them (check on uptodate for specific drugs) but a couple examples are:
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
High doses and rapid infusion of medications
1-3 weeks after offending drug
Influenza-like symptoms (malaise, myalgias, arthralgias) x 1-3 days
Conjunctival itching or burning
Acute onset macules over face, trunk, may form flaccid bullae
Positive when shear stress on the skin i.e. rubbing results in exfoliation. Indicates a pathology at the dermal/epidermal junction.
Staphylococcal scalded skin syndrome
Asboe-Hansen sign (AKA bullae spread sign)
Mucous membrane involvement.
Eyes, mouth lesions
Mortality with SJS is 10%, TEN 30%
Supportive care for skin
Prevention of vulvovaginal sequelae
Evaluate for loss of surface epithelium
Saline rinses to remove debris
If extensive sloughing, then amniotic membrane transplantation (prokera ring)
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:
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)
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)
Fever and rash emergencies:
Subacute bacterial endocarditis
Rocky Mountain Spotted Fever
Toxic epidermal necrolysis
Toxic shock syndrome (staph aureus or GAS)
Varicella zoster (VZV)
Primary infection – chickenpox
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
Vasculitis (medium to large vessel vasculopathy)
More common in immunocompromised hosts and frequently fatal
Diarrhea, pharyngitis, otitis media
For healthy children <12 ⇒ nothing
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)
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