Kikuchi disease

Kikuchi disease is an uncommon disorder characterized by benign cervical lymphadenopathy and fever. The pathogenesis is thought to be immunologic in nature perhaps as a response to an unknown infectious agent. It is most common in young females who were previously healthy. It was first recognized in Asian patients but has been seen in all ethnicities. Systemic symptoms such as fatigue, joint pain, rash, night sweats, and weight loss can also happen. Diagnosis is made by LN biopsy (with characteristic findings), and many patients will also need to be evaluated for other autoimmune disorders (SLE, etc) and indolent infection (TB, fungal, etc). Interestingly, it is typically self-limited  and resolves within a few months.

 

Author: Dr. Jeremy Brooksbank

References:

  1. Asano S, Akaike Y, Jinnouchi H, et al. Necrotizing lymphadenitis: a review of clinicopathological, immunohistochemical and ultrastructural studies. Hematol Oncol 1990; 8:251.
  2. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. Medicine (Baltimore) 2014; 93:372.

TB and HLH

A patient from Mexico was admitted as a transfer to gen med and was diagnosed with disseminated TB and later developed HLH a few days after starting steroids and RIPE therapy. We talk a lot about malignancy and autoimmune disorders triggering HLH/MAS, however infections can cause it as well. Viruses are the most frequently implicated specifically EBV, CMV, parvovirus, herpes simplex virus, varicella-zoster virus, measles virus, HHV- 8, H1N1 influenza virus, and HIV either alone or in combination. TB (often if disseminated) is a known but uncommon trigger for HLH. Interestingly, patients may be more likely to develop this severe complication right around the time they receive steroids or start RIPE therapy.

Here is a review from 2017 of 8 patients with TB and HLH.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406066/
PMID: 28422850
An earlier (2015) review from India can also be found at the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663863/.
Other bacterial (Gram negatives like Brucella), fungal, and parasitic infections have also been identified as being a trigger for the development of HLH but are quite uncommon.
Author: Dr. Jeremy Brooksbank (based on a case by Dr. Dennis Narcisse)
References: as above

Fibromyalgia

–  When you approach someone who endorses 10/10 pain but otherwise appears well, start with getting a basic history of the pain including onset, location, etc.

–  Ask about their sleep habits (sleep deprivation can cause multiple organic symptoms including pain, abdominal discomfort, etc.)

–  Screen for depression (“just like tired brains don’t deal with pain very well, depressed brains don’t deal with pain very well”)

–  Ask about trauma, abuse, home safety, etc.

– On exam, look for evidence of concomitant autoimmune disorders (joint swelling, rash, etc.)

– The diagnosis of fibromyalgia is entirely clinical based on a questionnaire (attached) that asks about location of pain in major muscle groups (Widespread Pain Index or WPI) and associated symptoms of poor sleep, fatigue, depression, etc. (SSS). This pain and symptoms cannot be due to another disorder.

 

Try to focus on three big topics when discussing treatment strategies of fibromyalgia:

1) Sleep hygiene

– Evaluate for OSA

– Consider medications including melatonin, trazodone, TCAs, or cyclobenzaprine

2) Exercise

–  30 minutes of aerobic exercise three times per week

– Encourage your patients to start slowly

– Structured exercise is more helpful than unstructured, so if possible refer to PT.

– The Duke Center for Living has a good arthritis rehabilitation program.  Other community resources for low-impact exercise include the YMCA and the Edison-Johnson public pool

3) Reassurance
       – Explain to your patient that fibromyalgia will not lead to joint destruction and exercise will not make it worse
       – Consider CBT if covered by insurance
Use Dr. Criscione-Schreiber’s explanation: “If you slice your finger, there is a signal that goes from your finger to your brain which tells you ‘pain in your index finger.’”  You also hear about shark attacks at the beach, someone can be bitten by a shark and swim back to shore without noticing pain until they get somewhere safe – why is that?  There are signals that are come down from the brain to ‘block’ the pain sensation.  Two things seem to happen in fibromyalgia:        – Painful signals are not getting blocked on their way up to the brain

– ‘Wires can get crossed’ – if someone pushes on their arm it shouldn’t hurt. In fibromyalgia that signal somehow gets ‘crossed’ and interpreted as pain

Dr. Criscione-Schreiber and Dr. Robertshaw

Outpatient Management of suspected CVA/TIA

– Patients who present in the outpatient setting with stroke-like symptoms or a recent (72 hours) TIA should be admitted to the hospital if their ABCD2 score is >2 or if there is uncertainty whether the diagnostic workup can be completed within 48 hours (so basically everyone)

– ABCD2 risk score:

– age 60 years and older (1 point)

– blood pressure (systolic >140 or diastolic >90) (1 point)

– clinical features (unilateral weakness 2 points, speech impairment only 1 point)

– duration (60+ minutes 2 points, 10-59 minutes 1 point)

– diabetes (1 point)

– The most important aspect of treatment for patients with lacunar infarcts is secondary prevention
    – Aggressive blood pressure control
    – High-intensity statin
    – Anti-platelet therapy with DAPT for three weeks followed by monotherapy thereafter
Author: Dr. Callie Berkowitz

07/30/19 Drug-induced ANCA-associated vasculitis

Drug-induced ANCA-associated vasculitis (AAV)

Definition: self-explanatory. Drug-induced vasculitis associated with ANCA positivity

Epidemiology: uncertain incidence and prevalence but increases with duration of use/dose of inciting medications

Clinical features: mostly constitutional sx’s such as generalized fatigue, small-vessel vasculitis rash, arthralgias/arthritis, weight loss. Overall, often more mild than other ANCA vasculitides although some severe complications like crescentic GN and DAH have been described.
– commonly +for anti-MPO (P-ANCA) in high titers; so should be on differential if suspecting MPA or EGPA (Churg-Strauss)
– common to have Ab’s against elastase or lactoferrin
– much less common to be + for anti-PR3 (C-ANCA)

Causative Agents:
– Hydralazine (most common)
1. Drug-induced SLE: +anti-histone Ab, rash, joint involvement. Often spares kidneys and responds to cessation of drug alone (occasionally needs steroids alone)
2. Drug-Induced AAV: +anti-MPO, +anti-dsDNA, +/- anti-histone, more common to have renal involvement with pauci-immune GN

  • Drugs to treat hyperthyroidism: PTU (primarily) but also methimazole and carbimazole)
  • Minocycline, cefotaxime, isoniazid, rifampicin
  • Procainamide, clozapine, phenytoin, indomethacin

Treatment:

  • primarily treated by discontinuation of offending medication: if mild may resolve after stopping the med
  • More severe cases (especially if lung or kidney involvement) require high-dose steroids with long taper courses +/- cyclophosphamide or other immunosuppressants
  • Developing: In general, there is evolving evidence that more prognostic information is based on MPO-AAV and PR3-AAV rather than the disease classification themselves.

Author: Dr. Jeremy Brooksbank

 References:

1. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.
2. A.K. SHORT, C.M. LOCKWOOD; Antigen specificity in hydralazine associated ANCA positive systemic vasculitis, QJM: An International Journal of Medicine, Volume 88, Issue 11, 1 November 1995, Pages 775–783

08/09/19 Splenomegaly

Splenomegaly as detected on physical examination is relatively rare (~3% in otherwise healthy adults), however the certain patient populations have significantly higher prevalence of splenomegaly (for example, ~10-15% post-partum and up to 65% with HIV).

The spleen participates in hematologic and immunologic functions and abnormalities are often traumatic or pathologic. One should always evaluate for splenomegaly in the cases of suspected or proven viral illness (particularly EBV), malignancy, or lymphoproliferative disorders. Additionally, patients with cirrhosis/other portal HTN, malaria, and select connective tissue disorders may also have splenomegaly.

Grover, et al published an interesting article in JAMA in 1993 which describe different methods of detection of splenomegaly on physical examination and clinical implications. More recent evaluation as part of the Rational Clinical Examination series looked at the likelihood ratios of palpations vs percussion for detection of splenomegaly with the following findings.

Below is a diagnostic schematic from CPS for splenomegaly which is useful when considering various causes of splenomegaly.

Splenomegaly – Schema

 

Author: Dr. Jeremy Brooksbank

References:

Splenomegaly. In: Simel DL, Rennie D. Simel D.L., Rennie D Eds. David L. Simel, and Drummond Rennie.eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis New York, NY: McGraw-Hill; 2009.

Grover SA, Barkun AN, Sackett DL. Does This Patient Have Splenomegaly? JAMA. 1993;270(18):2218–2221

07/30/19 Pancytopenia

Pancytopenia has a interesting differential diagnosis, and a structured format can be helpful in remembering the various causes. Below we list the 3 “buckets” of pancytopenia.

Bone marrow infiltration/replacement – Such disorders include hematologic malignancies (eg, leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes), metastatic cancer, myelofibrosis, and infectious diseases (eg, miliary tuberculosis, fungal infections).

Bone marrow aplasia – Nutritional disorders (eg, deficiencies of vitamin B12 or folate, Cu, Zn), aplastic anemia, infectious diseases (eg, HIV, viral hepatitis, parvovirus B19), immune destruction, and medications are among the causes of marrow aplasia.

Blood cell destruction or sequestration – Excessive blood cell destruction occurs in disseminated intravascular coagulation, thrombotic thrombocytopenia purpura, and ineffective hematopoiesis (eg, myelodysplastic syndromes, megaloblastic disorders), while excessive sequestration may be due to hypersplenism (eg, from liver cirrhosis, storage diseases, lymphoma, or autoimmune disorders).

Authors: Dr. Nathan Goodwin and Dr. Jeremy Brooksbank

07/31/19 Atrial Septal Aneurysm

Atrial septal aneurysms are redundant/mobile septal tissue that move during the cardiac cycle and are often an incidental finding or echo or other cardiac imaging (about 1-2% of population; TEE much more likely to detect than TTE; Case review of 195 cases found 47% of septal aneurysms were missed on TTE: Circulation. 1995;91(11):2785.). However, they can be associated with cerebral ischemic events and cardioembolic phenomena. In a prior study of patients with ischemic CVA and normal carotid arteries, 28% of these patients were found to have atrial septal aneurysms [Eur Heart J. 2001;22(3):261.] They commonly can be associated with increased rates of PFO and ASD. 

Interestingly, intracardiac shunt has been detected in ~75% of patients with atrial septal aneurysm. Also, as predicted, there are higher rates of atrial arrhythmias including Afib.

Endocarditis does not seem to be more frequent in these patients, but has been case-reported in the past. Here is a case of a patient with both right&left sided endocarditis due to translocation across septal aneurysm with PFO.

[J Echocardiogr 2005; 3: 153-155]

See the image below for as atrial septal aneurysm

This is different from apical aneurysms of which there are two type:

  • LV aneurysm: can be congenital but more commonly post-MI. Therapy depends on size but generally consists of afterload reduction + warfarin if thrombus is present. Refer to surgery for aneurysmectomy (which is just a great word) if refractory HF or arrhythmias.

2. LV pseudoaneurysm: made of only part of the LV wall and therefore weaker with 30-50% of rupture -> need surgical correction.

 

Author: Dr. Jeremy Brooksbank

07/31/19 Elevated high-sensitivity troponin in sepsis

There are numerous causes of elevated troponin in hospitalized patients. A common occurrence on general medicine service is in the setting of bacteremia and sepsis. With the onset of high-sensitivity troponin, the percentage of abnormal troponins has risen in many clinical settings. Elevated troponin is associated with worse outcomes in sepsis. Here is a German study from 2014 which used hsTnT in the ED and looked at the frequency of hsTnT elevation in sepsis identified in the ED.

[Clin Res Cardiol. 2014 Jul;103(7):561-7; PMID 24535379]

Older data showed the estimated prevalence of positive troponin in the context of sepsis from a meta-analysis in 2015 is 61% (CI 58–64%). Elevated troponins in sepsis are felt to be more than just mismatch in supply and demand as seen below:

Possible pathogenic mechanisms for sepsis-induced troponin elevation.

Causes of troponin elevation in the context of sepsis Proposed pathogenic mechanism of troponin elevation
1. Demand–supply mismatch Tachycardia, hypoxemia, hypotension, decreased oxygen delivery, ↓coronary perfusion pressure
2. Direct myocarditis Bacteremia → cytokine and endotoxin release → microvascular dysfunction, bacterial myocarditis, myocardial depression and ↑myocardial cell membrane permeability
3. Free radicals and superoxide radicals Sepsis → activation of NADPH oxidases complexes → formation of free radicals → myocardial cell damage and apoptosis
4. Elevated filling pressures and ventricular wall  stress Activation of intracellular signaling cascade → cardiac myocytes apoptosis, myocytes damage and micronecrosis; reduced coronary perfusion pressure
5. Left ventricular diastolic and right ventricular  systolic dysfunction _
The chart above was taken from [J Intensive Care Soc. 2015 Feb; 16(1): 52–57.] 
 
Here is a nice meta-analysis with additional information below.
[Prognostic value of troponins in sepsis: a meta-analysis: Intensive Care Med. 2013 Jul; 39(7):1181-9. PMID 23595497]
Author: Dr. Jeremy Brooksbank
References:
Clin Res Cardiol. 2014 Jul;103(7):561-7
 J Intensive Care Soc. 2015 Feb; 16(1): 52–57.
Intensive Care Med. 2013 Jul; 39(7):1181-9.

08/07/19 Resistant HTN

Some recent guidelines from the AHA on resistant hypertension management:

 
Specifically related to spironolactone:
  • Recent reports document the efficacy of mineralocorticoid receptor blockade (Figure 3, step 3, and Table 4) to improve BP in patients with RH.373–377 In patients who are not overtly volume overloaded but who have evidence of low renin status or salt sensitivity of BP, mineralocorticoid receptor antagonists (spironolactone or eplerenone) are more successful than α- or β-blockers.373,377 Spironolactone has the advantage of once-daily administration and can be initiated at doses of as little as 12.5 to 25 mg daily. However, the use of spironolactone as a fourth drug is limited by tolerability issues in some patients, including the development of hyperkalemia in those with CKD with an eGFR <45 mL·min−1·1.73 m−2 or baseline serum potassium >4.5 mEq/L.378 Approximately 70% of adults with RH are candidates for mineralocorticoid receptor antagonists based on eGFR and serum K+, yet only a small fraction receive these effective agents.379 With prolonged use at higher doses, gynecomastia and erectile dysfunction in men and menstrual irregularities in women may limit the use of spironolactone. In such cases, eplerenone may be used successfully.380 Because of its shorter half-life compared with spironolactone, eplerenone should be administered twice daily for optimal effect.
Here’s a nice flowsheet that is similar to the recommendations Dr. Kourany mentioned:
Figure 3. Algorithm depicting the management of resistant hypertension. BP indicates blood pressure; CCB, calcium channel blocker; and RAS, reninangiotensin system. *These diuretics maintain efficacy down to estimated glomerular filtration rates (eGFRs) of 30 mL·min−1·1.73 m−2. **Use caution if eGFR is <30 mL·min−1·1.73 m−2. ***Requires concomitant use of a β-blocker and diuretic. ****Requires the concomitant use of a β-blocker and loop diuretic.
Author: Dr. James Deardorff