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Rheumatoid Arthritis and Acute Asthma Exacerbations - 8/23/2012

posted Aug 23, 2012, 8:45 AM by Rohit Das   [ updated Dec 27, 2012, 7:02 AM by Purnema Madahar ]

A lot of good “bread and butter” medicine today…At resident report, Mary Gover, blessed with another interesting case, presented a woman in her 50s presenting with classic Rheumatoid Arthritis. Let’s review some of the key clinical points for this relatively common illness:

  • Pathogenically, RA is extremely complex. Clinically apparent disease is thought to be a combination of genetics (particularly HLA foci), unknown reasons behind repeated activation of innate immunity, and environmental effects. Smoking is particularly contributory, which with the right genes, can increase susceptibility to RA by 20-40 fold. A fairly complex review article on the pathophysiology of RA is attached, if you’re interested…
  •  From an epidemiology standpoint, the prevalence of RA is about 0.5 to 1%, is more common in women (about 3 times), and incidence peaks in women older than 65.

Most classically, RA presents as an insidious (>4-6 weeks) polyarticular inflammatory arthritis, typically involving small joints (MCPS, PIP, wrists, MTPs) early in the disease, and joints of the upper and lower limbs later on. However, presentations are often atypical. RA can present acutely (up to 1/3 of patients). Episodic symptoms, termed “palindromic,” progresses to full blown RA in ~70% of patients. Very rarely, patients may have a monoarticular presentation, heralding the presentation of full blown RA later in their course. There are also a whole host of “extra-articular” manifestations (page 1098-99 on the Lancet article), which occur in about 40% of patients with RA, and is a marker of disease severity (generally, only patients with marked joint manifestations will have extra-articular disease).  

There are diagnostic criteria for RA, which have been revised as recently as 2010, mainly in order to pick up, and treat, RA earlier in its course. The top right hand corner of Figure 2 in the Lancet article displays the criteria, which focuses on the extent of joint manifestations, serology, acute phase reactants, and duration of symptoms. With a cutoff of 6, several studies have looked at the accuracy of the 2010 criteria, as compared to the 1987 criteria (top left hand corner of Figure 2):

  • In the attached study from Arth & Rheum, the sensitivity of the 2010 criteria was 70-80%, and the specificity was similar – 60-70%. Unfortunately, I could not find a study looking at the accuracy at different cutoff values…
  • At baseline evaluation, 68% of patients who fulfilled the 2010 criteria DID NOT fulfill the 1987 criteria. The point here – the new criteria is picking up RA earlier in its course.

Deciding to treat RA, and what to treat with, is based on assessments of disease severity. There are several tools and multiple things to take into account, and the Lancet reviews them fairly nicely. Regarding management, some things to take into account:

  • The majority of patients with RA have progressive disease, though 10% have prolonged remissions, and 15% can have intermittent courses that obviate the need for continuous therapy.
  • One of the key concepts you’ll see a lot is “tight control,” which advocates for frequent severity assessment, consequent step-up of therapy if needed and achieving remission. It also advocates for initiation of DMARDs as early as possible, even in patients with early, mildly active RA. Up to 50% of patients with progressive disease will achieve remission with appropriate therapy. 
  • Dr. Jain nicely went through several of the different treatment options, including DMARDs (like MTX, Hydroxychloroquiine, Leuflonomide), anti-TNF biologics, and non-anti TNF biologics. 
  • The goals of treating RA are to minimize joint inflammation and therefore prevent joint destruction, and to prevent functional decline. Mortality in patients from RA is mainly due to cardiovascular events and infection (RA patients are relatively immunocompromised, in part due to the therapies that are given for the disease). Patients with RA are also at increased risk of lymphoma/lymphoproliferative disorders.

At intern report with Dr. C, asthma exacerbation, in the setting of a community-acquired PNA, was the topic of conversation. Also a lot to talk about here. I’ll focus on a couple of little tidbits for inpatient asthma management that I find interesting...

  • Though we always use nebulizer treatments for patients in the ED and on the floors, please realize that MDIs are probably just as good as, if not better, than nebulized treatments. In a prospective study comparing nebulizer with MDI/spacer, the two did not differ in hospital admission rates, but the latter led to shorter stays in the ED, lower relapse rates, and a better improvement in peak flow.
  • We often see acute asthma being managed with inhaled B-agonists AND anticholinergics in the ED…there is a lot of data on this topic, with some studies supporting its use, and others not. The most recent expert recommendations advocate FOR Atrovent, though only for use in the ED, and not on inpatient floors…
  • What about Magnesium? By supposedly preventing calcium influx with smooth muscles cells of our airways, Mg does have bronchodilator activity, especially in severe asthma. Of the randomized trials I came across, in the majority of patients, Mg DOES not impact hospital admission rates and other important clinical outcomes. However, in subgroup analyses of one meta-analysis, there is potentially some benefit for patients with severe asthma attacks (Peak Flow <200, pulsus paradoxus, hypoxia/hypercapnia…etc.)…

Bottom line – B-agonists and steroids are the mainstay of acute asthma treatment, with anticholinergics and Mg as potential adjuncts, especially in severe attacks. It’s very important to remember to try to transition to MDI as soon as possible, as not only are they more effective, but it also allows for direct observation and education around proper MDI (and spacer if necessary) use…which is the best way, by far, to keep asthmatics out of the hospital.

..Also, Dr. Conigliaro wrote:

So I cannot find anything on how or if to taper steroids in asthma. I think our pt got methylprednisolone based on several studies which found that giving steroids in the ER reduced the need for hospitalization, and particularly giving them within one hour of arrival to er. The benefits were greatest for pts not already on steroids.
Also, there is a recommendation by  the Expert Panel II Report, which recommends 120 to 180 mg/d of either prednisone, methylprednisolone, or prednisolone in 3 or 4 divided doses for 48 hours, then 60 to 80 mg/d until the PEFR reaches 70% of predicted or the patient’s personal best. Whether this is the best strategy is unclear. In one meta-analysis, Manser and colleagues found no therapeutic differences between low-dose corticosteroids (≤80 mg/d methylprednisolone or ≤400 mg/d hydrocortisone) and higher doses in hospitalized patients.
Haskell and coworkers compared 3 doses of methylprednisolone (15, 40, and 125 mg) IV every 6 hours for
3 days. The high-dose group improved by the end of the first day, the medium-dose group improved by the middle of the second day, and the low-dose group failed to improve by day 3. Finally, Bowler and colleagues found no difference between hydrocortisone 50 mg IV four times daily for 2 days followed by lose-dose prednisone and 200 or 500 mg of hydrocortisone also administered four times daily for 2 days followed by high dose prednisone. Oral steroids are as effective as parenteral steroids, but less desirable in patients at risk for intubation.

So you see, not everything in medicine is known!

Thanks Dr. C! And yea, not everything in medicine is known, which is what makes it AWESEOME...

Hope this was useful…and for the consistent readers, I’d love some constructive feedback as we quickly approach next month…Enjoy your weekends!



The Pathogenesis of Rheumatoid Arthritis
McInnes et. al., NEJM 2011, Volume 365: 2205-19

Scott et. al., Lancet 2010, Volume 376: 1094-1108

van der Linden et. al., Arth & Rheumatism 2011, Volume 63(10): 37-42

Newman et. al., Chest 2001, Volume 121: 1036-1041