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.
- 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
- Hepatic sequestration
- Viral hepatitis
- Iron overload from transfusions
- Sickle cell intrahepatic cholestasis
Acute SCD complications
- Severe anemia (due to splenic sequestration, aplastic crisis, or hyperhemolysis)
- Vaso-occlusive phenomena
- Renal infarction or med toxicity
- Dactylitis/bone infarction
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
- Use of accessory muscles of respiration
- Chest pain
- 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)
- SpO2 >90% on RA
- 1 lobe affected by infiltrates
- SpO2 >85%
- 2 lobes affected
- Respiratory failure à mechanical ventilation
- 3 lobes affected
- 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%)
- For CAP and atypicals x 7 days
- Supplementary O2
- Incentive spirometry
- DVT ppx
- 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
Today, we talked about a middle aged man presenting with acute onset of abdominal pain and weight loss, found to have a consolidation on chest imaging, low SAAG ascites, and a nodular omentum, work up revealing disseminated cocci! For more cases like this, check out http://www.humandx.org. If you’d like to hear some expert diagnosticians take a crack at this case and learn from their reasoning, check out thecurbsiders.com.
- Patients with immunosuppression, pregnancy, and DM2 are at risk of developing disseminated cocci.
- The most common manifestation of cocci is pneumonia which can be consolidative, nodular, or cavitary. Other manifestations include the skin (erythema nodosum and erythema multiforme), joints (arthralgias, vertebra, osteo), meningitis, SSTI, and visceral organs (rare).
- Cocci should be on your differential of infections that can cause eosinophilia and a low SAAG ascites.
Approach to eosinophilia
- Neoplasm ⇒ hypereosinophilic syndrome, T cell lymphoma, hodgkins lymphoma, solid organs (cervical, ovarian, gastric, colon, and urothelial cell carcinoma)
- Allergies ⇒ atopy, medication induced
- Adrenal insufficiency ⇒ rare cause
- Connective tissue disease ⇒ EGPA (formerly known as Churg Strauss), RA
- Parasites: strogyloides, toxocara, lymphatic filariasis, isospora, dientamaeoba, sarcocystis (note Giardia does NOT cause eosinophilia)
- Viruses: HTLV, HIV
- Fungi: aspergillus (ABPA), cocci, paracocci, histo, crypto
- Primary eosinophilic syndromes (typically single organ involvement of eos, may not have blood eosinophilia) ⇒ eosinophilic fasciitis, eosinophilic cellulitis
Differential for ascites based on SAAG
- Peritoneal carcinomatosis
- Infections (tuberculosis, bacteria, fungi including cocci, schistosomiasis)
- Biliary ascites
- Portal HTN
- Liver (cirrhosis, acute failure, alcoholic hepatitis, budd chiari, mets)
Coccidioidomycosis: Refer to this prior post on our blog for more details.
- Airborne fungal infection transmitted by cocci immitis and cocci posadasii
- Geographic distribution is southwest US and central valley
- Most common time for transmission is summer and fall seasons
- Risk factors for developing severe disease
- Immunosuppression (HIV with CD4 <250, steroids, chemo)
- DM2 (more likely to develop cavitary disease)
- Clinical manifestations
- Incubation period is 7-21 days
- Primary manifestation is CAP
- Other manifestations
- Skin: erythema nodosum and erythema multiforme
- Joints: arthralgias (desert rheumatism), osteo of joints and vertebrae
- Visceral organs and omentum (rare)
- Imaging (CXR can be normal in 50% of patients)
- Cocci EIA to screen
- Cocci immunodiffusion and complement fixation to confirm
- Immunocompetent and minimal symptoms? No treatment, most resolve spontaneously
- Severe disease/disseminated
- First line is fluconazole or itraconazole
- If no response, can try posaconazole
- Last resort is amphotericin B
- Duration of treatment can be up to a year
- Repeat anti-coccidioidal Abs in 2-4 weeks after starting treatment to ensure treatment response
Joe presented the case of a young man from Mexico with unknown immunization history who presented with acute onset of AMS, fevers, and a progressive vesicular rash, diagnosed with primary varicella infection (chickenpox!), now in the ICU with varicella pneumonia and likely varicella vasculitis induced stroke.
- Vaccinate your kids!
- Two main VZV presentations are primary infection (chickenpox) and reactivation (shingles, disseminated zoster in immunocompromised individuals)
- Varicella rash presents as vesicular lesions at varying stages. Vesicular lesions at the same stage of development are concerning for smallpox.
- The most common complication of primary VZV in adults is pneumonia. Treatment is with IV acyclovir.
- The most common neurologic complication of primary VZV is encephalitis. No approved therapy exists.
- Isolation precautions for shingles is contact. For disseminated zoster or chickenpox, make sure you patient is on contact and airborne precautions.
Differential for fever, rash, and pharyngitis:
- Mono (due to EBV, CMV, toxo, HHV6)
- Acute HIV
Fever and rash emergencies:
- Subacute bacterial endocarditis
- Rocky Mountain Spotted Fever
- Necrotizing fasciitis
- Toxic epidermal necrolysis
- Toxic shock syndrome (staph aureus or GAS)
Varicella zoster (VZV)
- Primary infection – chickenpox
- Clinical manifestations:
- Prodrome of fever, malaise, pharyngitis, loss of appetite
- Rash is often pruritic and occurs in successive crops over days (new vesicle formation stops after 4 days). Vesicular lesions at varying stages on an erythematous base on the trunk, face, and extremities.
- send swab (from ulcer base) for HSV PCR and DFA. These have quick turn around time and high sensitivity. Viral culture takes weeks and is less sensitive.
- Most common complications
- Children: skin infection
- Pneumonia (1/400 cases) with a mortality of 10-30%. In people requiring mechanical ventilation, mortality reaches 50%.
- Risk factors for pneumonia development are cigarette smoking, pregnancy, immunosuppression, and male sex.
- Develops 1-6 days after the appearance of rash
- CXR usually with diffuse bilateral infiltrates with possible nodular component in early stages
- Prompt administration of acyclovir has been associated with clinical improvement
- Encephalitis: acute cerebellar ataxia (more common in children), diffuse encephalitis (more common in adults)
- No proven therapy once encephalitis occurs. Acyclovir has been used with anecdotal success
- Transient focal deficits
- Aseptic meningitis
- Transverse myelitis
- Vasculitis (medium to large vessel vasculopathy)
- More common in immunocompromised hosts and frequently fatal
- Diarrhea, pharyngitis, otitis media
- For healthy children <12 ⇒ nothing
- For adults
- if no complications, then oral valacyclovir (1g TID) or acyclovir (800 mg 5 times/day)
- if immunocompromised ⇒ treat with IV acyclovir if active lesions present (10mg/kg q8h)
- if complications
- acyclovir IV 10mg/kg q8h for 7-10days
- contact and airborne precautions!
- Reactivation – shingles
- Clinical manifestations –
- Rash – most common location is thoracic and lumbar dermatomes
- Localized, painful and restricted to a dermatome
- Disseminated if > 3 contiguous dermatomes or 2 dermatomes on separate parts of the body, painful
- Acute neuritis – 75% of patients have pain/burning/throbbing prior to onset of rash
- Complications in immunocompetent hosts –
- post-herpetic neuralgia (most common), superficial skin infections, ocular complications (acute retinal necrosis and zoster ophthalmicus), motor neuropathy, meningitis, Ramsay hunt syndrome (zoster oticus)
- For patient with localized disease presenting <72 hours after clinical symptom onset, treat with oral acyclovir, valacyclovir, or famciclovir
- For patient with localized disease presenting >72 hours after disease onset, then monitor
- Pregnant women, treat with acyclovir
- Disseminated disease, treat with IV acyclovir
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!
- 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
- Raynaud’s phenomenon
- Mechanic hands
- Non-erosive arthritis
- ILD: Often severe and rapidly progressive, frequently predominates other symptoms
- Cardiac arrhythmias or ventricular dysfunction
- Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
- Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
- 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
- Most common findings are traction bronchiectasis, GGO
- Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.
- 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.
- Chronic steroids: osteoporosis, PJP prophylaxis if > 20mg > 1 month
- Hep B reactivation
- Azathioprine: Check TPMT levels!
- 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
Our case today is a 49 year old woman with no medical history, presenting with 1 month of difficulty swallowing, voice changes, and more recently dysphagia with liquids and solids, and shortness of breath. Her symptoms are worse during the night time to the point that she couldn’t swallow her own spit/secretions. She presented with respiratory failure requiring intubation, and on CXR/CT she was found to have an anterior mediastinal mass concerning for a… thymoma!
Let’s first briefly review Myasthenia Gravis before moving onto Myasthenia Crisis, and lastly, Thymomas.
- Bimodal: Early peak in 2-3rd decades (female predominance) and late peak 60-80s (male predominance).
- F in post-partum period have inc risk.
- Possible association with: neuromyelitis optical, autoimmune thyroid disorders, SLE, RA.
- Ice-pack test: Improvement of ptosis after application of an ice pack = positive. Sensitivity around 80ish %, limited to patients with ptosis and not helpful for those with extraocular muscle weakness.
- Source: NEJM, Grepmed
- Edrophonium test is no longer used very often, in a nut shell, it is a Acetylcholinesterase inhibitor with rapid onset (within 30-45 seconds), produces improvement of affect muscles after injection.
- 80-90% sensitivity but high rates of false positive. Not very specific.
- Serology (seropositive in 90% of MG patients).
- AChR Ab
- Titers do not correlate with disease activity
- 85% positive in generalized MG
- Highly specific, extremely low false positives (LE, certain motor neuro dz, polymyositis)
- Seen in 38-50% with generalized MG who are AChR Ab negative.
- Thymoma patients with MG: 98-100% will have positive AChR-Ab.
- NPPV for thymoma in the absence of AChR-Ab is 99.7%
- Seronegative: 6-12%, more likely to have purely ocular myasthenia.
- EMG: Can help confirm diagnosis
- Single fiber EMG
- Abnormal in > 90% of those with generalized MG, less so in ocular MG
- Most sensitive diagnostic test for MG, 90-95% sensitivity (les for ocular MG), 91% specific.
- Repetitive nerve stimulation
- Readily available but less sensitive vs SFEMG
- Nerve is stimulated multiple times, and the compound muscle action potential is recorded, test is considered positive if progressive decline in CMAP readings with the first 4-5 stimuli.
- Sensitivity 75-80%
- Symptomatic: Pyridostigmine, max daily dose 7mg/kg
- Too much pyridostigmine can cause cholinergic crisis, leading to—weakness. Chances of this dec by limit daily dose of pyridostigmine to less than 960mg daily
- Chronic immunotherapy: Required for those with sx on pyridostigmine or recurrence of sx on pyridostigmine after initial improvement.
- Steroids or immunosuppressives i.e. azathioprine, mycophenolate, cyclosporine.
- Thymectomy: Recommended for age < 60, has been considered beneficial even without presence of a thymoma.
Definition: Weakness severe enough to impair muscles of respiratory requiring mechanical ventilation.
- 10-20% of pts with MG will experience at least one crisis, annual risk 2-3%
- For 13-20% of pts with MC, the crisis is their first clinical manifestation of MG and initial diagnosis.
- Most occur in the first few years after diagnosis of MG.
- Progressive generalized or bulbar weakness leading to respiratory failure.
- Variable presentation in terms of degree of weakness (general vs respiratory)
- May be precipitated by: infection, surgery, pregnancy, childbirth, medication tapering, certain drugs (beta blockers, antibiotics), magnesium
- Airway/Breathing: Monitor respiratory muscle strength frequently, should be admitted to MICU
- Indications for intubation:
- FVC < 15 – 20 mL/kg
- NIF < -25 to -30 cmH2O (i.e. 0 to -24)
- Respiratory fatigue
- PCO2 > 50
- Difficulty with secretions
- Intubation if signs of impending respiratory failure.
- Elective intubation, rather than emergent, is preferred.
- Rapid IVIG or plasma exchange, FAST
- Plasmapheresis directly removes acetylcholine receptor ab in the circulation
- High dose glucocorticoids, azathioprine, cyclosporine, or mycophenolate
- Wean as respiratory muscle strength improves after completing or IVIG or plasma exchange.
- Aggressive pulmonary toilet.
- Pyridostigmine generally avoided after intubation temporarily since it might increase secretions, leading to more complex pulmonary care.
- Can be resumed after extubation.
- Median age 40-60
- Men ~ Women
- No known risk factors but strong association with myasthenia gravis
- Local thoracic symptoms
- Paraneoplastic symptoms
- Up to ½ of pts with thymoma will have MG like sx.
- MG is common with thymomas but rare in thymic carcinoma
- Neuro: MG, polymyositis, Lambert Eaton, Isaac’s syndrome, stiff person syndrome
- Heme: Pure red cell aplasia, hemolytic anemia, pernicious anemia, agranulocytosis
- Derm: Alopecia areata, pemphigus, scleroderma, vitiligo, oral lichen planus
- Endo: Addison’s disease, Cushing syndrome, panhypopit, thyroiditis
- Other: Nephrotic syndrome, RA, sarcoid, hepatitis, hypogammaglobulinemia, myocarditis
- CT and/or MRI
- Carcinoma findings: Necrotic, cystic, or calcified, irregular contour
- Definitive dx requires tissue biopsy
- Masaoka staging system vs American Joint Committee on Cancer (AJCC), with the former being more commonly used.
- Surgical resection: as much as possible, including complete resection of the thymus. Potentially curative.
- If extensive disease, can consider chemo followed by radical resection +/- RT for potentially resectable cases.
- If complete resection cannot be done, maximal debulking followed by post-op RT.
- Potential phrenic nerve damage due to tumor expansion or surgery. Can sacrifice one for surgical resection but if both are involved, then it’s a more complicated discussion.
- Main determinant = staging and complete resectability of the tumor
- Most commonly used staging system = Masaoka Staging System
- Masaoka stage I and II: Favorable
- Masaoka stage III: 27% recurrence after complete resection, 62% with incomplete resection. 10yr survival 83%
- Masaoka stage IV: 10-yr survival is 47%
Tim presented a young man with no medical history presenting with a chronic cough with intermittent trace hemoptsis. Other than this cough and mild shortness of breath when he exerted himself, this pt had no other symptoms. A CXR revealed bilateral pleural effusion, and upon thoracentesis, milky fluid drained out with an elevated triglyceride content consistent with a chylothorax. Subsequent biopsy of a lymph node revealed a diagnosis of follicular lymphoma!
Since we are talking about pleural effusion, Light’s Criteria will inevitably come up. For both real life (and boards!) purposes, know this criteria really well!
- SENSITIVE but NOT SPECIFIC for exudative effusions.
Any one of these criteria = exudative
- Fluid protein/Serum protein > 0.5
- Fluid LDH/Serum LDH > 0.6
- Fluid LDH > 2/3 upper limit of normal of serum LDH
False positive is possible in certain settings:
- Chronic diuretic use can falsely elevate fluid LDH (KNOW THIS)
- Transudative effusion that’s been sitting there chronically can appear exudative like
The following tests can help us distinguish between a falsely positive exudative effusion from a true exudative effusion:
- Pleural cholesterol > 45 mg/dL has high sensitivity and specificity for exudative effusions.
- Can also use serum albumin – fluid albumin < 1.2g/dL to confirm exudative effusion
Pleural Fluid Analysis: Clues
Upon performing a thoracentesis, certain characteristics can potentially give us some clues to the etiology of the effusion…
Fluid WBC Count
Fluid Predominant Myelocyte Type
Lastly, how do you diagnose a chylothorax and what are some potential causes?
- Definition: Triglyceride > 110 mg/dL = slam dunk
- 50 – 110: Less clear, cannot rule out, obtain liproprotein analysis. If presence of chylomicron is detected, likely chylothorax
- < 50: Less likely
- Malignant: Lymphomatous is most common, can also be other cancers i.e. lung, mediastinal mets, sarcoma, leukemia
- Non-malignant: Idiopathic, benign tumors, protein losing enteropathy, thoracic aortic aneurysm, TB, Sarcoid, amyloidosis, thyroid goiter, tuberous sclerosis, congestive heart failure, mitral stenosis
- Surgical is most common
- External trauma
- Trivial “trauma:” Stretching while yawning, coughing, hiccupping, sneezing (I’m not kidding)
Management of a malignant pleural effusion, as seen in this case, can be potentially challenging. After the patient was discharged, his pleural effusion on the right recurred within 3 days and completely filled up his right lung!
Several options are available for management of malignant pleural effusions. The decision is complicated and will goals of care discussion
- Indwelling pleural catheter
- Advantage: Pt managed, can drain at home
- Disadvantage: Catheter related complications
- Talc, slurry or poudrage, is the preferred agent. 60-90% success rate in reducing recurrence at 30 days.
- Doxycycline can also be used but not as popular any more
- Advantage: Eliminates the potential space for fluid reaccumulation
- Disadvantage: Pain, potential for surgical failure, invasive
- Combination: Talc + IPC
Katie presented a case of an elderly man with history of non-anuric ESRD on HD three times a week, NIDDM2, CMML, Klinefelter Syndrome, HTN, chronic anemia, and prior GIB secondary to gastric AVM who presented with shortness of breath. Earlier during the day he was at the transfusion center where he received a unit of PRBC. He was restless after the transfusion but he refused to stay for post-transfusion monitoring. He has been compliant with dietary restrictions and his HD sessions, but that evening after he went home, he started having difficulty breathing and hence he came to the ED. He was significantly hypertensive on presentation, and he went into respiratory failure requiring NIPPV. CXR revealed significant bibasilar pulmonary infiltrates c/w pulmonary edema. After diuresis and dialysis, his symptoms resolved. This presentation is consistent with transfusion associated circulatory overload, or TACO!
Let’s use this case to go over different types of transfusion reaction since you:
- Will encounter this during your career
- Will definitely get paged about this on nights
- Might encounter the more rare but potentially life-threatening reactions
- Common presentation
- Fever (defined as > 1 degree Celsius from baseline)
- Stable: Likely febrile non-hemolytic transfusion reaction
- Tylenol, slow rate of infusion, observe
- ABO incompatibility
- Bacterial contamination
- Hemolytic transfusion reaction
- TA Graft vs Host Disease (4-30 days after, delayed rxn, attack by immunocompetent donor lymphocytes on an immunocompromised recipient’s antigen presenting tissues. In immunocompetent recipients, reaction can occur if recipient is heterozygous for an HLA for which the donor is homozygous)
- Mild allergic reaction to plasma protein, common, resume transfusion at slower rate, anti-histamine PRN.
- Dyspnea or hypoxia
- Assess for anaphylaxis
- Yes: Treat for anaphylactic allergic reaction
- No: Consider circulatory overload
- E/O vol overload, diuretic responsive: TACO (transfusion related circulatory overload)
- Signs of instability, diuretic non-responsive: Suspect TRALI
- Hemolysis 1-4 weeks after transfusion: Delayed hemolytic transfusion reaction, usually very mild
Epidemiology: 1% of transfusions in general, higher in the ICU.
Pathophysiology: Circulatory overload leading to pulmonary edema
- Preexisting renal or cardiac dysfunction
- Higher transfusion volume
- Small stature
- Low body weight
- Extremes of age
- Development of respiratory distress or hypertension during or within 6 hours of completing a transfusion.
- May see concurrent headache
- Hypoxia, HTN, tachycardia, wide-pulse pressure, JVD, S3, crackles/wheezing
- Nt-proBNP elevated but non-specific
- Stop transfusion
- Report to transfusion service or blood bank. Get consultation for future transfusions i.e. smaller units, lower volume, or only during dialysis
- Rare, estimated 1 in 12000, leading cause of transfusion related mortality in the US
- Seen in all age groups and both sexes
- Not completely understood, but thought to be a neutrophil mediated reaction in setting pre-existing endothelial injury in the lungs, or antibodies to HLA
- ICU patients
- Multiparous female donors (OR 4.5)
- Heme malignancies
- Chronic EtOH
- Liver dysfunction
- Tobacco use
- Positive fluid balance
- Mechanical ventilation
- Note: Transfusion of older blood products was once thought to be a risk factor, but disproved by multiple RCTs around 2010-2012.
- During or within 6 hours after blood product transfusion
- Hypoxia, pulmonary infiltrates on exam, fever, hypotension
- May see elevated peak/plateau airway pressures in vented patients
- Non-responsive to diuretics
- ARDS like picture, sometimes diagnosis can be unclear, recent nomenclature of transfused ARDS.
- May have coexisting TACO
- Stop transfusion
- Notify blood bank/transfusion service
- Oxygen/ventilatory support, ARDS protocol (lower tidal volume) has generally been used
- Hemodynamic support, pts often hypovolemic, give fluids, pressors if needed.
- Corticosteroid historically has been used with inconsistent results
- Mortality as high as 41-67% in ICU population. Non-ICU patients have much lower morality, 5-17%. Almost all will recover their resp function, and they can still safely receive blood transfusions in the future.
- Identify implicated donor
- Irradiate blood products for immunocompromised recipients
- Avoid transfusion of blood product from a relative
- Blood donated by men has lower incidence for unclear reasons
Sarasa presented a case of a young woman with recently diagnosed pulmonary TB on HREZ presenting with worsening dyspnea and voice changes. Her fiberoptic endoscopy of the upper airway was normal. She was found on CT to have tissue thickening and stranding in the mid/lower trachea as well as a small tracheal diverticula, very suspicious for endobronchial TB!
Definition: TB that involves the tracheobronchial tree
- More common among patients with extensive pulmonary TB, especially with cavitary lesions, can occur in 10-40% of patients but less common now with anti-TB therapy.
- For some reason more likely to occur in women in second to third decades of life.
- Usually seen in main and upper bronchi, but in 5 % of cases: involves the lower trachea
- Unclear but thought to be by either direct extension of pulmonary disease into the bronchi, spread via infected sputum, or hematogenous/lymphatic spread.
- Cough, CP, hemoptysis, wheezing (low pitch), fatigue, fever, dyspnea. Can mimic foreign body aspiration, non-resolving pneumonia, or malignancy.
- Can have significant sputum production, leading to bronchorrhea (> 500mL/day of sputum)
- Complications: Atelectasis, obstruction, bronchiectasis, tracheal stenosis, fistula, hilar lymph node rupture
Diagnosis: CT and bronchoscopy are methods of choice for dx, with bronch being the most validated for confirming the diagnosis.
- XR: Can be normal in 10-20% of cases
- CT: Can demonstrate endobronchial lesions, stenosis (up to 2/3 of patients), or fistulas.
- Bronchoscopy: able to visualize stenosis and biopsy. Can interview if severe symptomatic stenosis.
- Same as for other forms of TB but also prevent tracheobronchial stenosis
- Medical Therapy
- Intensive Phase: HREZ (aka RIPE) x 2 months
- R: Rifampin
- I: Isoniazid
- P: Pyrazinamide
- E: Ethambutol
- Continuation Phase
- Ex: 2HREZ/4HR = standard regimen, 2 months of HREZ (RIPE), followed by 4 months of isoniazid and Rifampin
- Specific for endobronchial TB
- Corticosteroids: Controversial.
- Shown improvement in outcome (prevention of bronchial compression) in children.
- Some data on shortening healing time and decrease severity of bronchial stenosis
- Nebulized INH or streptomycin, mixed data
- Surgery: Usually indicated for stenosis or stricture. Balloon dilatation, stenting, ablation, resection, cryosurgery.
- Severe tracheobronchial stenosis sometimes requires pneumonectomy or lobectomy
Distinctive entity, also more prevalence in younger patients, most commonly presents with dysphonia (96%), odynophagia (25%), and stridor (9%). True vocal cords, epiglottis, and false vocal cords are most commonly involved.
Drug Resistance and TB
- Drug-resistance TB: resistant to one or more anti-TB drugs
- Mono-resistant: single agent
- Poly-resistant: resistant to multiple drugs, but susceptible to either INH or rifampin but not both
- MDR: R to INH and rifampin + others.
- XDR-TB: Extensively drug resistant TB: resistant to INH, rifampin, fluoroquinolones + either aminoglycosides or capreomycin or both.
1st Line Agents
2nd Line Agents
- Fluoroquinolones (Levofloxacin, Moxifloxacin)
- Injectable: Amikacin, Capromycin, Kanamycin
- Other: Cycloserine, Linezolid, Ethionamide
Bedaquiline, Para-aminosalicyclic acid, imipenem, meropenem + Augmentin, thioacetazone.
If suspecting resistant, strategy usually is to add at least 2 additional drugs. Adding single drug inc risk for resistance.
Management of drug-resistant TB:
Tx of MTB PCR will be based on susceptibility data
- Conventional: 20-26 months treatment, with an intensive phase with at least 5 effective drugs for at least 6 months after negative sputum, followed by a continuation phase of at least 4 drugs for 18-24 months
- Shorten version for 9-12 months if no extra-pulmonary manifestation and susceptible to quinolones.
Please refer to this informative article on a review of endobronchial TB.
Thanks to Barnie for presenting the case of a middle-aged woman who was admitted with acute onset of SOB, found to have submassive PE.
- Risk stratification tools are helpful in estimating the pre-test probability of PE. The best and most validated is Wells criteria.
- YEARS items is a newer tool that was studied in an RCT in the Netherlands and found to lower the number of CTPA scans ordered by 14% without a significant impact on rates of missed PE diagnoses.
- For patients at low risk of PE according to Wells, PERC is useful in ED or outpatient setting to rule out PE without ordering a d-dimer (see graphic below).
- Age-adjusted d-dimer is age x 10 for patients older than 50 years. This accounts for the increase in d-dimer baseline related to aging. ADJUST-PE trial showed that age-adjusted d-dimer leads to higher specificity without subsequent VTE.
- Studies have shown an 11.6% reduction in CTPA scans with the use of this correction factor without an appreciable increase in missed diagnoses of PE.
- Think of PE in three broad categories:
- Massive PE = hemodynamically unstable ⇒ anticoagulation + thrombolysis
- Submassive PE = hemodynamically stable + RV strain ⇒ anticoagulation + thrombolysis
- Low risk PE = hemodynamically stable, no RV strain ⇒ anticoagulation. Use the PESI score to determine if your patient can be treated outpatient.
- Remember that the most common EKG finding in PE is normal sinus rhythm! The most common abnormal EKG finding is sinus tachycardia. S1Q3T3 pattern is only seen in 10% of patients with PE.
Suggested algorithm for diagnostic work up of suspected PE:
Remember that the scoring tools above are only there to add to your clinical judgment, not replace it!
Recent study in the Lancet looked at the utility of a different diagnostic algorithm, using the three most predictive items on Wells together with d-dimer. Compared to Wells, this diagnostic tool led to a 14% reduction in unnecessary CTPA!
- Remember that clot burden does not factor into the treatment categories of PE. Low clot burden in a patient with baseline cardiopulmonary disease can still lead to hemodynamic compromise and would be considered massive PE.
- Submassive PE treatment is an area of much debate. A famous trial (PEITHO trial) in 2014 randomized 1006 patients to receive heparin + placebo vs heparin + tenecteplase (European version), and found a >50% reduction in combined death and cardiovascular collapse at 7 days but a > four-fold increase in risk of major bleed including intracranial hemorrhage. Subsequent meta-analyses (and this one) found that the risk of major bleeding was highest in people >65 years of age. So treatment decisions here are tricky and require consulting multiple services!
Signs of RV strain:
- EKG findings:
- S1Q3T3: this is a sign of cor pulmonale and can be seen in a number of conditions in addition to PE
- Bronchospasm (really bad asthma)
- Echo findings:
- Elevated RVSP
- Septal bowing
- McConnell’s sign (regional wall motion abnormality sparing the RV apex)
- Not sensitive but helpful in distinguishing RV strain due to chronic pulmonary HTN from RV strain due to acute PE
- Increased RV size
- Decreased RV function
- Tricuspid regurgitation
- Elevated troponin
- Elevated BNP
Thank you Charles for presenting this really interesting case. A 18 year old woman with a history of asymptomatic thrombocytopenia who presents with several days of non-specific fever, chills, malaise, mild shortness of breath and she was found to have acute anemia, thrombocytopenia, elevated transaminitis, and patchy bilateral pulmonary infiltrates on CXR during initial presentation. She became acutely ill with submassive hemoptysis and went into respiratory failure in 24-48 hours. She was found to have DAH on BAL. Her autoimmune and infectious work up came back negative, but her ferritin came back at 75776. Base on this and her constellation of symptoms, further work up revealed a 6/8 criteria for diagnosis of hemophagocytic lymphohistiocytosis!
- Dyspnea, cough fever, respiratory failure, acute anemia
- Hemoptysis only in 2/3 of cases
- Definition: Hemoptysis, diffuse alveolar infiltrates, acute anemia, and hypoxemic respiratory failure
- Widespread damage to pulmonary small vessels, leading to blood within the alveoli eventually causing impaired gas exchange.
- Causes: Autoimmune/connective tissue disease leading to pulmonary vasculitis (ANCA, anti-GBM), certain pulmonary infections, toxins, drug reactions, mitral stenosis in some cases
- 3 distinct histologic subtypes that can give hints to underlying pathology
- Most common: Pulmonary capillaritis: ANCA vasculitis, GPA, EPGA, pauci-immune, Goodpasture, HSP, SLE, RA, APLS, MCTD, Behcet, drug-induced, lung transplant rejection, etc.
- Systemic vasculitis manifestation
- Bland pulmonary hemorrhage: Coagulopathy, mitral stenosis, toxin/inhalation, SLE, drugs, Goodpasture
- Anti-GBM, SLE, no inflammation or destruction of capillaries but RBC leakage
- Diffuse alveolar damage: BM transplantation, radiation, ARDS, cytotoxic drugs, other causes
- CXR: Diffuse bilateral alveolar infiltrates, no pathognomonic findings
- BAL: serial bloody aspirate with sequential sampling
- CT: Non-specific GGO
- Biopsy: Tissue biopsy of the lung is definitive in confirmation of DAH but underlying cause might not be revealed.
- Treat underlying cause
- Respiratory support, most patients die from respiratory failure
- High dose corticosteroids, i.e. methylprednisolone up to 500mg Q6H (up to 2g daily)
- Other agents: Cyclophosphamide, azathioprine, MTX, mycophenolate, etanercept.
- Plasmapheresis for Goodpasture or vasculitidies.
- Key: Early identification and treatment
- Worldwide incidence is unknown, not enough data available, thought to be rare AND underrecognized but growing recognitive leads to higher incidence.
- Familial types: more common to occur in pts < 18yo
- Secondary HLH: any age
- Uncontrolled hyperinflammatory response with dysregulated macrophage activity leading to excessive cytokine production
- Primary: HLH due to an underlying genetic abnormality or without clear cause
- Autosomal recessive familial HLH
- Secondary: Due to something else
- Retrospective study at Mayo in 2014:
- Infection (34%), most commonly EBV
- Autoimmune (8%), Macrophage activation syndrome (MAS), most often associated with AOSD, systemic juvenile idiopathic arthritis, or SLE.
- Malignancy (52%) NHL, HL, acute leukemia
- Idiopathic/Immune deficiency/other (6%)
- Fever, splenomegaly, cytopenias are most common
- + manifestation of the trigger
- Complications: Infection, DIC, bleeding complications (reports of intracranial hemorrhage, GIB, DAH), end organ damage.
Diagnosis: Per the Histiocyte Society: 5/8 criteria for diagnosis. In case you cannot remember all 8, please refer here for the famous HLH Song by Dr. Eric Lau:
- Peripheral cytopenia (> 2 cell lines)
- Hypertriglyceridemia or Hypofibrinogenemia
- Elevated ferritin > 500 (> 10000 = 90% sensitive and 96% specific for HLH)
- Low NK cell activity
- Elevated soluble CD25 (soluble IL2-R)
- Hemophagocytosis in BM, spleen, or LN: Only seen in later course of the diseases and not required for the diagnosis, neither sensitive nor specific, can be seen in severe sepsis/critical illness)
- Like all things in medicine, treat the underlying cause
- Current treatment is based on the HLH-94 study on pediatric population
- Induction: 8 weeks dexamethasone and etoposide.
- Maintenance: Cyclosporine, tacrolimus, dex pulses
- If MAS: Steroids alone, usually responsive.
- Hematopoietic stem cell transplant is refractory/relapsing.
For more information on HLH, please refer to this article by Dr. Schram and Dr. Berliner published in Blood (as in the journal) in 2015.