Recurrent AIDP vs CIDP vs sensory GBS variant 2/4/2019

Thank you Julie for presenting a case of a 27yo F with a history of Guillain Barre syndrome 2 years ago, requiring 1 year of rehab but now with full neurological recovery, presenting with numbness and tingling of her lower extremities and her hands. Her symptoms are described as “ants crawling” on her skin, which started at her feet but became progressively more superior. Also endorses involvement of her hands as well later on. She has no recent illnesses and she has no illicit drug use. Her first episode of GBS started out very similarly, hence she was concerned.

EMG revealed a primarily demyelinating polyneuropathy affecting motor > sensory nerves predominantly in the lower extremities… but wait, does it even fit her symptoms, which are primarily sensory (although mild subjective weakness)???


We will use this case to illustrate that there is a spectrum of Guillain Barre!

GBS

Epidemiology

  • All age groups affected but risk increases with more advanced age
  • M > F slightly
  • Most commonly associated with after an episode of campylobacter jejuni infection.
  • Other culprits: VMC, EBV, HIV, Zika virus, Mycoplasma.
  • Rare cases of GBS can happen after a triggering event, i.e. immunization, surgery, BMT.

Pathophysiology

  • Immune response to a preceding infection that cross-reacts with peripheral nerve leading to demyelination (a form of molecular mimicry)
  • Note that there are two forms of peripheral neuropathy:
    • Axonal
      • Pathophys: Disruption of the axon itself, typically presents with motor >>> sensory deficits.
      • DDx: HIV, amyloidosis, B12 deficiency, Lyme disease, hypothyroidism, critical illness polyneuropathy, variant of GBS
    • Demyelinating
      • Pathophys: Disruption of the myelin sheath, slowing nerve conduction velocity. Both sensory and motor deficits would be present.
      • DDx: GBS (classic), hereditary, infectious, drugs, certain monoclonal gammopathies.
  • Picture1.jpg

Variants of GBS include but are not limited to…

  • AIDP (Acute Inflammatory Demyelinating Polyradiculoneuropathy)
    • Most common form, (85-90%)
    • Disease activity usually nadirs by 4 weeks
    • Progressive ascending symmetric weakness due to inflammatory demyelination
    • 2-5% may develop CIDP
  • CIDP (Chronic Inflammatory Demyelinating Polyradiculoneuropathy)
    • Disease progression or relapses lasting longer than 8 weeks
    • Most of the time does not have an antecedent/preceding event.
  • Miller Fisher Variant
    • 10-20% of cases
    • Typical presentation: ophthalmoplegia, ataxia, areflexia.
    • 25% will develop some extremity weakness
    • 85-90% of pts with MFS will have GB1b antibodies positivity, strongly associated with involvement of oculomotor nerves.
    • If presence of encephalitis: Bickerstaff encephalitis, possibility a spectrum of anti-GQ1b antibody syndrome.
  • Acute motor axonal neuropathy (AMAN): Axonal form of GBS
    • More rapid progression motor wise but sensory and DTR usually preserved.
    • Most cases preceded by campylobacter infection as well
    • Frequent in Asia and esp in Hong Kong, more prevalent in the summer
    • More severe form is AMSAN (Acute motor and sensory axonal neuropathy)
  • Pharyngeal-cervical-brachial variant
    • “Localized” version of GBS
  • Pure Sensory GBS
    • Primarily sensory deficits with mild motor deficits.

Presentation

  • Timing: Progresses over 2 weeks, most cases start improving by 4 weeks. IF post-infection, sx can develop after days to weeks.
  • Progressive symmetric ascending muscle weakness starting in the lower extremities and then spread upward.
  • 10% of the time, muscle weakness starts in arms or facial muscles.
  • Absent to depressed DTR seen in all cases
  • Respiratory muscle weakness requiring ventilator support in 10-30% of cases
  • 80% of patients will experience paresthesias of the hands and feet accompanying motor weakness.
  • Neuropathic pain.
  • Dysautonomia in 70% of cases (tachycardia, HTN/Hypotension, bradycardia, ileus, urinary retention, arrhythmias, can also see SIADH.

Diagnosis

  • CSF: LP recommended to support dx
    • Elevated protein (45-200 typically but can be as high as >1000 mg/dL) with nrl WBC (albuminocytologic dissociation), seen in 50-66% in the 1st week after onset of sx, >75% of pts in the 3rd
    • CSF cell count typically nrl, < 5 cells/mm3, in a minority of cases can expect to see mild elevation.
  • EMG: Valuable for confirming dx but can be nrl early on the disease course.
  • GQ1b antibody: associated with Miller Fisher variant
  • MRI: Spinal MRI may reveal enhancement of spinal nerve roots and cauda aquina.

Management

  • Secure airway!
    • Predictors of respiratory failure: inability to cough, stand, lift the head, lift the elbows, and liver enzyme elevation.
    • Avoid succinylcholine in intubation, increased risk of hyperkalemia.
  • Supportive care, DVT prophylaxis, bladder/bowel care, PT/OT, pain control
  • Plasma exchange/IVIG is indicated in most cases, speed up recovery.
    • Plasma exchange usually more effective when started within 7 days of sx onset. 4-6 tx over 8 days.
    • IVIG: 0.4g/kg per day x 5 days.
    • IVIG and plasma exchange also recommended for ambulatory patients who are still not seeing improvement of sx after 5 weeks.
  • No role of steroids!

Prognosis

  • Full motor recovery around 60% at 1 year. Recovery can take several years.
  • 2-5% develop CIDP
  • 3-7% mortality rate, 20% of patients who become ventilator dependent die of complications.

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