The Man With Recurrent Leg Swelling

 Saw an interesting case last week.

Thirty-two year old Caucasian man, works loading-unloading shlelves in a supermarket. Over several months, has had recurrent episodes of swelling in his right lower foot, extending from shin, across the ankle into the dorsum of foot. During the episodes, which last several hours, the leg feels very swollen, tight and uncomfortable but not much actual pain.

As usual GP thought of gout, checked urate levels- plumb normal. Does a MRI of the ankle after a normal X-ray. That just shows subcut fluid, joint looks fine. Inflammatory markers normal.

Chap comes to Rheumatology clinic. I get a bit more history. Turns out that the episodes always happen after lunch when he goes back to his rather manual role at the supermarket. He usually has various types of sandwich for lunch.

Has he ever had anything else that seemed unusual? Turns out that in the past, on several occasions, when he had a can of Fosters (a type of lager), his throat felt swollen "inside", so that he would struggle to swallow for hours afterwards, although there was no shortness of breath. He now avoids lager.

The penny drops. The guy has a fascinating condition called "Food Dependent, Exercise Induced Anaphylaxis" (FDEIA). Most published cases in the literature have been in conjunction with wheat consumption, followed shortly afterwards by exercise. Except that now we realise that it's not just exercise, but alcohol and NSAIDs that can trigger this after subjects have fed.

Although in most cases, the putative food contains wheat, other allergens that can trigger it are celery, mustard, fenugreek and coriander. Celery and mustard are of course widely added to spice up pizzas and other takeaways and therefore may be hidden.

You might have guessed that the episodes of "swelling" inside the throat and the leg, both represent angioedema, the first mucosal, the second cutaneous.

This is now called augmentation factor anaphylaxis or cofactor associated food allergy. Avoidance works best, but of course, sometimes the specific food trigger can be hidden, and therefore difficult to identify.

Interestingly celery interacts with birch pollen and a couple of other pollen to give rise to what is described as "Pollen Food Allergy". These people with apparent hay fever, get anaphylaxis type episodes every time they ingest celery.

Such people sgould avoid food that contain a very high concentration of fruit pulp such as smoothies, as the latter is apparently rich in something called Lipid Transfer Protein (LTP), which is very allergenic.

They should also consider carrying an EpiPen, just in case...

Mycoplasma hominis & Ureaplasma urealyticum Cause Septic Arthritis in Subjects with Hypogammaglobulinemia

 If you have a subject with hypogamma, either due to CVID or other "constitutional" causes, such XLA, or acquired, due to immunosuppression, usually with Rituximab, who present with a picture of inflammatory arthritis, either monoarthritis or oligoarthritis, suspect infection by either Mycoplasma hominis or Ureaplasma urealyticum, particularly if usual cultures are negative and the usual antibiotics do not work.

Both organisms are overrepresented in subjects with septic arthritis developing against a background of hypogamma, particularly on Rituximab. The most commonly affected joints are hip, knee, shoulder, elbow, ankle and PIP. Prosthetic joint infections, particularly affecting the hip have been reported several times.

These fastidious organisms will not grow on routine cultures. M.hominis may show up on anaerobic culture plates after 5 days, but is best cultured on PPLO (pleuropneumonia like organism) broth or looked for by 16S RNA. Similarly, U.urealyticum is best cultured on Ureaplasma differential agar, Ureaplasma broth, or A7B agar. Fortunately, the last 3 will also grow M.hominis. U.urealyticum can also be identified on 16S RNA analysis.

If a person with hypogamma and putative inflammatory arthritis has proven culture negative on synovial fluid and blood culture, do ask for these special media or 16S RNA to isolate these 2 organisms. 

Ureaplasma requires urea in its culture medium for growth. It produces urease with breaks down urea into ammonia, and can thus change the colour of phenol red to pink. M.hominis metabolises arginine, but not glucose. Ureaplasma ferments neither, but produces a "managanese reaction" in culture.

If the usual antibiotics have not worked, there would be a natural tendency to attribute the inflamed joint(s) to the underlying disorder such as RA or Lupus, or make a new diagnosis of one of the above two, and treat with steroids. This may lead to a worsening of such arthritis, so special caution is warranted in subjects with hypogamma.

A course of doxycycline may be indicated if the usual antibiotics which target cell walls (which these organisms lack) have not worked. Resolution of fever/arthritis with doxycycline supports the likelihood of infection by one of the above two.