Bilateral Panuveitis 1/31/2019

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!

In Summary:

  • 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:

eye

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

  • Infectious:
    • HSV:
      • Usually unilateral, might have other clues such as presence of vesicles.
    • Toxoplasmosis:
      • Ocular toxoplasmosis for some reasons occurs more frequently in immunocompetent hosts.
    • Lyme Disease
    • Syphilis:
      • 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.
    • CMV:
      • 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
    • Sarcoidosis
    • IBD
    • Ankylosing spondylitis
    • Relapsing polychrondritis:
    • Behcets
    • 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
    • Vogt-Koyangi-Harada(VKH)Syndrome:
      • Japanese and Hispanics, bilateral panuveitis, neurological/auditory sx
    • Penetrating trauma
    • Drug-induced:
      • Rifbutin, fluoroquinolone, monoclonal ab
  • Other conditions that might mimic uveitis
    • Retinal tears
    • Ischemia
    • Leukemia
    • Lymphoma
    • Ocular melanoma
    • Pigmentary dispersion syndrome
    • Retinitis pigmentosa
    • Retinoblastoma

Management

  • 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!

Cryptogenic Organizing Pneumonia 1/30/2019

Wendy presented a case of a middle age woman presenting with 4-6 weeks history of cough, shortness of breath, subjective fever and chills, non-improving after three courses of antibiotics. She was treated multiple times for presumed atypical CAP (bilateral infiltrates on CXR), and she presented again with worsening respiratory failure. Her infectious work up so far has been negative. CT Cx revealed bilateral infiltrates mainly in the peripheral lower lung zones.


Let’s go over non-resolving pneumonia and “typical pneumonia” for a little bit first.

“Typical” Pneumonia

  • Typically see sx improvement within 3-5 days of appropriate tx.
  • Vitals and O2 requirement expect to improve in 2 days
  • Fatigue and cough may take 2+ weeks to resolve.
  • Radiographic improvement usually takes weeks to months to clear up

If your patient is not improving within an expected time frame, then it’s time to broaden that differential! (The following are just some suggested ddx to consider)

Non-infectious causes (20% of the time)

  • Neoplasm:
    • Bronchogenic carcinoma, endobronchial obstruction secondary to mass effect, lymphoma
  • Inflammatory:
    • Vasculitis: GPA, pulmonary alveolar hemorrhage
    • Eosinophilic pneumonia
    • Acute interstitial pneumonia
    • Bronchiolitis obliterans organizing pneumonia (BOOP) or cryptogenic organizing pneumonia (COP)
      • Subacute, 75% of pts have sx < 2 months prior to diagnosis, flu like presentation initially mimicking an atypical pneumonia, patchy infiltrates also mimics pneumonia on chest radiograph.
    • Sarcoidosis
    • Connective tissue disease
    • Rare: Pulmonary alveolar proteinosis, plastic bronchitis
  • Drug-induced: Amiodarone, nitrofurantoin, chemo
  • PE
  • Pulmonary edema in abnormal lung architecture i.e. severe bullae seen in COPD patients.

Infectious causes

  • Streptococcus pneumoniae PNA: responsible for most cases of non-resolving infectious causes due to complications, i.e. multi-lobar involvement, drug resistance, co-morbidities.
  • Legionella
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae
    • Risk factors: SNF, military recruits
  • Haemophilus:
    • Risk factors: Elderly, immunocompromised
  • TB: Always on the DDx here.
  • Fungi: Always on the DDx here.
    • Aspergillus
    • Histo
    • Blasto
    • Cocci
    • Crypto
  • Nocardia
  • Actinomyces
  • PJP (HIV history)
  • Löffler’s syndrome
  • Complicated infection
    • Abscess (EtOH, poor dental hygiene at risk for anaerobes), might need prolonged course of abx.
    • Empyema: More likely in younger patients and those with illicit drug use

Diagnostic Approach in non-resolving cases of “pneumonia”

  • Assess for risk factors for delayed resolution, i.e. age, medical co-morbidities, pneumonia severity, and the pathogen involved.
  • If non-resolution, repeat history, assess for clues for atypical pathogen or non-infectious etiology. Ask if you’re treating the right bug if you’re sure that it’s an infectious cause (i.e. fungal?)
  • At this point, consider Chest CT and additional tests as needed. If CT is non-diagnostic, consider:
    • Bronchoscopy with BAL +/- transbronchial biopsy
    • CT-guided FNA if e/o LAD or lesion
    • Last resort: Consider surgical lung biopsy

Cryptogenic Organizing Pneumonia

Pathophysiology

  • Idiopathic diffuse interstitial process affecting distal bronchioles, alveolar ducts + walls leading to alveolar epithelial injury.

Epidemiology

  • Unknown! But pts are typically 40-60s, equally reported in M and F.

Risk Factors

  • Unclear, condition is not that well understood.

Presentation

  • Subacute to chronic cough, dyspnea, fever, malaise, may have an acute flu-like phase followed by a prolonged persistent of milder symptoms.
  • Typically diagnosed as CAP but fail to response to empiric abx.
  • Most common features:
    • Persistent non-productive cough (72%)
    • Dyspnea (66%)
    • Fever (51%)
    • Malaise (48%)
    • Weight loss (57%)
  • Lung exam: Ranging from normal to crackles

Diagnosis

  • Labs: Non specific but 50% of pts p/w leukocytosis, and elevated ESR (>100) and CRP are seen in 70-80%
  • CXR: Bilateral, patchy infiltrates
  • HRCT:
    • Usually reveals patchy air-space consolidations, GGO, small nodular opacities, and bronchial wall thickening. Patchy opacities occur more frequently in the peripheral and lower lung zones.
    • Mediastinal LAD might be present in rare cases
    • Closely resembles chronic eosinophilic pneumonia
  • PFT: Restrictive most commonly. DLCO is reduced in majority of cases, indicating gas exchange abnormalities.
  • Bronchoscopy + BAL:
    • Findings typically non-specific in COP but mainly done to rule out other etiology.
    • BAL: Might see increased lymphocytes, neutrophils, and eosinophils with lymphocytes predominance.
  • Trans-bronchial Lung biopsy: Usually done to ID other disease processes, non-specific findings in COP mimicking ILD.
  • Surgical Lung Biopsy: Will need a large sample

Management

  • No major RCTS so generally tx decisions are based on guidelines, experience, and case series.
  • Mild dz: Observe
  • Persistent symptomatic/worsening:
    • Oral glucocorticoids, usually up to 100mg/day but typically 60mg daily starting, x 4- 8 weeks, then taper over 3-6 months.
    • Serial radiographs
    • Failure to response to steroids:
      • Cyclophosphamide can be considered
      • Cyclosporine
      • Rituximab
    • Long term glucocorticoid dependence:
      • Can consider steroid sparing agents i.e. azathioprine (TPMT level!)
    • Severe, respiratory failure: High dose steroids initially then transition to orals.

Prognosis:

  • 2/3 of pts respond well to glucocorticoids with complete resolution of sx.
  • 1/3 have persistent symptoms and pulmonary abnormalities
  • Overall, better prognosis compared to ILD!

Take Home Points:

  • Typical illness script is a patient (men & women equally) in his/her 40-60s presenting with a chronic pneumonia like clinical picture not improving on antibiotics.
  • Chest radiograph with bilateral patchy infiltrates involving small airways/alveoli wall predominantly seen in the lower peripheral lung zones.
  • Responds well in most cases to corticosteroids, but most cases will need a prolonged course.
  • Check out this article from Chest for more learning!

MS vs NMO!

Thanks to Amran for presenting the case of an elderly woman with history of “transverse myelitis” 10 years ago who presented with b/l leg weakness, numbness, and tingling, found to have several spinal cord enhancements as well as optic chiasm enhacement on T2 FLAIR imaging concerning for MS vs NMO!


Clinical pearls

  • MS and NMO most commonly affect women (2:1 and 10:1 respectively).
  • To meet diagnostic criteria for MS, patients must demonstrate CNS lesions in both space and time via clinical or MRI findings.
  • NMP affects the optic nerve and spinal cord much more so than the brain/brainstem.
  • Presence of AQP4 serum antibodies are specific to NMO.
  • Treatment for acute MS flare or NMO flare involves high dose steroids or plasma exchange.
  • The most effective chronic treatment for relapsing/remitting MS is natalizumab, not effective for NMO and may even be harmful.

Framework for myelopathies:

 

capture

Demyelinating diseases that present with myelitis:

capture2

Multiple sclerosis:

Epi

  • Most commonly affects young adults
  • Mean age of onset 28-31. Though can present between 15-50
  • Affects women 2:1
  • Life expectance is reduced by ~10 years

Presentation

  • Most common symptoms
    • Sensory disturbances (90%)
      • Numbness, tingling, pins and needles
      • Lhermitte sign (flexion of the neck causes sensation of electric shock that radiates down the spine into the limbs). Can be seen in tumors, cervical disk herniation, and trauma as well.
    • Fatigue and/or sleep disturbance (85%)
      • Unrelated to amount of activity performed
      • Worsened by depression
    • Motor issues and spasticity (80%)
      • Lower extremities most commonly affected
      • Paraparesis, paraplegia
    • Cognitive impairment (70%)
      • Attention, executive function, short term memory
      • Depression (60%) likely contributes
    • Bowel or bladder dysfunction (50-75%)
    • Visual disturbance (25%)
      • Internuclear ophthalmoplegia
        • Lost adduction and horizontal nystagmus of the abducting eye
        • Lesion in the medial longitudinal fasciculus of the brainstem on the side of diminished adduction
        • Convergence is preserved
      • Optic neuritis
        • Unilateral eye pain accentuated by ocular movement
        • Variable degree of visual loss (90% regain normal vision)
  • Characteristic features
    • Different types
      • Clinically isolated syndrome (first attack)
      • Relapsing-remitting
      • Secondary progressive
      • Primary progressive
      • Progressive relapsing
    • Heat sensitivity AKA “Uhthoff phenomenon” (80%)
      • Due to slowing of neuronal conduction with increased body temperature
  • Diagnosis
    • McDonald Criteria (revised in 2017)
    • Clinical or radiographic
    • CSF studies are not indicated unless atypical presentation
  • Treatment
    • Acute episode
      • Glucocorticoids
        • Solumedrol 1 g IV x 3-5 days
      • Plasma exchange
        • If failed glucocortidoids
    • Chronic
      • Disease modifying therapy
        • Good for relapsing-remitting MS

Cavitary lung lesions and SJS/TEN

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.


Clinical Pearls: 

  • 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

  • Infection
    • Pyogenic (necrotizing pneumonia, septic emboli, lung abscess)
    • Atypical (MTB, fungi)
  • Autoimmune
    • GPA >> RA, sarcoid
  • Malignancy
    • Liquid (lymphoma, KS, lymphomatoid granulomatosis)
    • Solid (squamous, GU>GI)
  • Vascular
    • PE
  • Other
    • 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)
    • AEDs
    • Allopurinol
    • Infx: Mycoplasma, graft-vs-host
    • Idiopathic
  • Risk factors
    • HIV (100x higher risk)
    • Genetics
      • 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
    • Malignancy
    • 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
    • Odynophagia
    • 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
          • SJS/TEN
          • Staphylococcal scalded skin syndrome
          • Pemphigus vulgaris
      • Asboe-Hansen sign (AKA bullae spread sign)
      • Mucous membrane involvement.
        • Eyes, mouth lesions
        • Respiratory sx
  • Prognosis:
    • SCORTEN score
    • Mortality with SJS is 10%, TEN 30%
  • Management
    • 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
      • Plasmapharesis
      • Anti-TNF

Bonus info on gout:

  • Acute flare:
    • Steroids
    • NSAIDs
    • 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
      • Probenecid
      • Lesinurad
    • Uricase
      • Pegloticase, fast improvement of symptoms, contraindicated in G6PD deficiency

Sickle cell disease and ACS

Today, Michael presented the case of a young woman with history of Sickle Cell Disease who presented with acute onset of CP, SOB, and pain, found to have new opacities on chest imaging and fevers concerning for Acute Chest Syndrome (ACS) with worsening symptoms requiring transfer for exchange transfusion.


Clinical Pearls

  • Leading cause of death in patients with SCD is acute chest syndrome (ACS)
  • ACS is defined as new radio density on chest imaging with fevers and/or respiratory symptoms.
  • Most common causes of ACS are bone marrow/fat embolism and CAP
  • There is no clinical/laboratory standard for diagnosing acute sickle cell crisis.
  • Hydroxyurea can decrease crisis frequency, ACS events, need for transfusions, hospitalizations, and death.

DDx of liver injury in the setting of SCD

  • Gallstones
  • Hepatic sequestration
  • Viral hepatitis
  • Iron overload from transfusions
  • Sickle cell intrahepatic cholestasis

Acute SCD complications

  • Infections
  • Severe anemia (due to splenic sequestration, aplastic crisis, or hyperhemolysis)
  • Vaso-occlusive phenomena
    • Pain
    • Stroke
    • ACS
    • Renal infarction or med toxicity
    • Dactylitis/bone infarction
    • MI
    • Priapism
    • VTE

Acute chest syndrome

  • Defined as a new radio density on chest imaging with fever (38.5) and/or respiratory symptoms
    • >2% decrease in SpO2 from a documented steady-state value on room air
    • PaO2<60 mmHg
    • Tahcypnea
    • Use of accessory muscles of respiration
    • Chest pain
    • Cough
    • Wheezing
    • Rales
  • Leading cause of death for patients with SC disease
  • Etiology of ACS in adults is commonly due to bone marrow or fat emboli followed by PNA
  • 50% of patients with SCD will have an episode of ACS
  • 80% of ACS episodes are associated with a vaso-occlusive pain episode
  • Morality rate is 4.3%
  • Clinical approach
    • Determine severity (affects treatment)
      • Mild
        • SpO2 >90% on RA
        • 1 lobe affected by infiltrates
      • Moderate
        • SpO2 >85%
        • 2 lobes affected
      • Severe
        • Respiratory failure à mechanical ventilation
        • 3 lobes affected
      • Treatment
        • Acute episode
          • Pain control
          • IVF (prevent hypovolemia but also avoid volume overload because it can worsen ACS)
          • Blood transfusion:
            • Mild ⇒ no transfusion
            • Moderate ⇒ simple transfusion
            • Severe ⇒ exchange transfusion (Goal Hg =10, HgS <30%)
          • Antibiotics
            • For CAP and atypicals x 7 days
          • Supplementary O2
          • Incentive spirometry
          • DVT ppx
        • Prevention
          • Hydroxyurea (decreased incidence of ACS by 50%)
            • Not good for acute episode
          • Chronic transfusion therapy
            • For those with > 2 episodes of moderate to severe ACS in 24 months despite hydroxyurea therapy

Disseminated cocci

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.


Clinical Pearls: 

  • 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/infections
    • 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

  • <1.1
    • Peritoneal carcinomatosis
    • Infections (tuberculosis, bacteria, fungi including cocci, schistosomiasis)
    • Pancreatitis
    • Biliary ascites
    • Serositis
  • >1.1
    • Portal HTN
      • Liver (cirrhosis, acute failure, alcoholic hepatitis, budd chiari, mets)
      • CHF

Coccidioidomycosis: Refer to this prior post on our blog for more details.

  • Micro
    • Airborne fungal infection transmitted by cocci immitis and cocci posadasii
  • Epi
    • 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)
    • Pregnancy
    • 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
      • Meningitis
      • SSTI
      • Visceral organs and omentum (rare)
  • Testing:
    • Imaging (CXR can be normal in 50% of patients)
    • Serologies:
      • Cocci EIA to screen
      • Cocci immunodiffusion and complement fixation to confirm
  • Treatment
    • 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

Varicella Pneumonia

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.


Clinical Pearls

  • 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:

  • Measles
  • Mono (due to EBV, CMV, toxo, HHV6)
  • Acute HIV
  • Parvovirus
  • Zoster
  • HSV
  • Mycoplasma

Fever and rash emergencies:

  • Meningococcemia
  • 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.
    • Diagnosis:
      • 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
      • Adults:
        • 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
        • Neurologic:
          • 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)
          • Hemiplegia
        • Hepatitis
          • More common in immunocompromised hosts and frequently fatal
        • Other
          • Diarrhea, pharyngitis, otitis media
    • Treatment
      • 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)
    • Treatment
      • 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

 

Seizure Secondary to Neurocysticercosis 1/14/2019

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.

Picture1.png

Presentation: Viable (asx, many years) -> degenerating (loses ability to evade immune system, localized inflammation) -> non-viable (calcified granulomas, can still cause szx)

  • Intra-parenchymal
    • 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.
  • Extra-parenchymal
    • 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…

Diagnosis

  • 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
    • Scolex.JPG

(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.

Management

  • 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
    • Ocular:
      • Surgery preferred over medical management.

A Beriberi Nice Case of… Thiamine Deficiency (1/9/2019)

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!


Thiamine deficiency

Epidemiology

  • Developing countries
  • Alcoholics
  • Extreme poverty
  • Displaced populations, refugees

Common Risk factors

  • Poor nutrition
  • Alcohol
  • 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.
        • 2/4
    • Korsakoff Syndrome: Memory loss, confabulation, +/-hallucinations

Pathophysiology

  • 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

Diagnosis

  • Clinical history
  • Thiamine level
  • Clinical improvement with thiamine administration
  • CT: May see classic atrophy in the mammillary bodies in Wernicke Korsakoff, highly specific.

Management

  • 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.

Prognosis

  • Most will have a degree of neurological deficits despite treatment.

Anti-Synthetase Syndrome 1/8/2019

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!


Anti-synthetase syndrome

Epidemiology

  • 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
  • Myositis
  • Raynaud’s phenomenon
  • Mechanic hands
  • Non-erosive arthritis
  • ILD: Often severe and rapidly progressive, frequently predominates other symptoms
  • Cardiac arrhythmias or ventricular dysfunction

Diagnosis

  • Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
  • Antibodies:
    • Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
    • Anti-PM-Scl
    • 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
  • CT:
    • Most common findings are traction bronchiectasis, GGO
  • Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.

Antibodies.png

Management

  • 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.

meds

Monitoring

  • Chronic steroids: osteoporosis, PJP prophylaxis if > 20mg > 1 month
  • Hep B reactivation
  • Azathioprine: Check TPMT levels!

 

Prognosis

  • 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