September 2005

A 13-year-old boy was admitted to the hospital for evaluation and treatment of a rash. About a week before admission, he was given a prescription for trimethoprim-sulfamethoxazole for the treatment of an upper respiratory infection. He took three or four doses before stopping on his own because of a rash that developed. He took over-the-counter diphenhy-dramine HCL without any improvement. A few days later, as the rash was becoming more severe, he was seen in a local emergency room, where he was treated with steroids (IM methylprednisolone and oral prednisone). However, the rash continued to become more intense, and he was referred for admission.

His past medical history is otherwise unremarkable and his immunizations are documented up to date.

Examination on admission revealed a well-developed, well-nourished 13-year-old boy with an obvious rash with a distribution as shown in figures 1–8. Of note are areas of blistering and some desquamation, especially on the face, and mucous membrane involvement of the mouth and eyes. The eyes also have a discharge.

Lab tests were unremarkable, including a complete blood count, electrolytes and urine analysis.

What’s Your Diagnosis?

1. Kawasaki disease
2. Erythema multiforme minor
3. Stevens-Johnson syndrome
4. Severe eczema

Answer

Why bring up an obvious case of Stevens-Johnson syndrome (SJS)? Answer: the startling rise of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). So, what does CA-MRSA have to do with SJS? Answer: many providers are going to sulfamethoxazole and trimethoprim (SMX-TMP) as their first drug of choice for managing soft-tissue infections presumed to be due to S. aureus, and if it happens to be a strain of CA-MRSA, there’s a good chance it will work.

However, I am concerned about this trend for a couple of reasons. One is obviously the risk of a severe rash as shown in this case. From a hospitalist standpoint, SMX-TMP is the number one trigger or cause of SJS in children admitted to our hospital, far out in front of herpes simplex infections (although it is clearly the most common infectious disease cause). And at the rate of SMX-TMP usage, we can expect to see a concomitant rise in these severe rash reactions. Another concern has to do with the spectrum of bacterial coverage of SMX-TMP for soft tissue infections. Not all are due to S. aureus. Some may be due to Streptococcus pyogenes (group A streptococci (GAS)), and SMX-TMP does not cover GAS, which actually can be more invasive and devastating than S. aureus. So while SMX-TMP is being empirically used, a possible GAS soft tissue infection could be moving along unchecked. I think once the organism is identified and sensitivities are known, then SMX-TMP can be a good choice, but in the initial days pending that information, I recommend using clindamycin. In our geographic area, it covers the vast majority of CA-MRSA, and if there’s a chance the soft tissue infection is due to GAS, well, clindamycin covers that too. If you live in an area where there is a lot of clindamycin-resistant CA-MRSA, you may need to have a different plan, which may include daily visits initially and a shorter fuse for admission and treatment with IV vancomycin till culture and sensitivity (C & S) reveal the information you need to continue therapy.

Obviously, the need to do cultures is more important than ever. If there is no pus to obtain and all you have is an area of cellulitis, there is a technique for doing a tissue aspirate for Gram’s stain and culture that has stood the test of time in years past, but has become somewhat of a lost art. My old friend, Ed Fajardo, MD, published a nice paper showing that performing a tissue aspiration from the area of maximal inflammation yields about 57% positive culture results, as opposed to aspirating the leading edge (4.8%), as was the practice with erysipelas in decades past. That brief report, found in the July 1987 issue of The Pediatric Infectious Disease Journal (pages 685-686), also describes the technique used. (See the comments section below for a description of the technique.)

Getting back to SJS, as noted above. I fear that we are going to be seeing more and more as SMX-TMP usage sores in the wake of the MRSA epidemic. So, we better review this complication a bit. Some experts refer to SJS as erythema multiforme major, which is usually distinguished from erythema multiforme minor (which is often confused with urticaria as shown in figure 9) by a more severe rash and involvement of at least two mucous membranes (usually the mouth and eyes). However, there is a growing opinion among dermatologists that these are separate entities, rather than a spectrum of the same syndrome. And they are probably correct, but proof of different entities rather than different manifestations in the spectrum of a syndrome, much like Kawasaki syndrome vs. incomplete Kawasaki syndrome, is difficult to come by. That being said, simple-minded people like me need some way to keep these severe rash syndromes straight. So, when I see a rash that looks like erythema multiforme, I look for mucous membrane inflammation, and if present, I get more concerned and watch for progression. The most severe form of this syndrome is often referred to as toxic epidermal necrolysis (TEN), which has similar features to SJS, but also has a deeper, subepidermal injury to the skin with more blistering (figure 10), a TEN patient previously treated with SMX-TMP). These patients are usually best treated in a burn unit, as shown in a different patient with a drug reaction in figure 11. A lot has been written about these “hot rashes,” much beyond the scope of this column. If you find yourself on the front line with one of these patients, ask your friendly dermatologist and/or infectious disease consultant for some help.

On the recommendation of the dermatology consultant in this case, steroids were continued. However, I am not aware of any evidence-based support for steroids in this condition. If you know of any, please write and let the rest of us dummies know.

Kawasaki disease does not result in blistering, vesicular or bullous lesions, or if it does, it must be rare. The rash is usually morbilliform (figure 12), but can consist of a variety of other rash types. The eyes of Kawasaki patients are inflamed without discharge. Also, even though the age limits on Kawasaki patients are expanding all the time, it would still be unusual at this patient’s age.

The word “eczema” is derived from the Greek word meaning “to boil out.” This is apparently how ancient observers perceived severe eczema, as shown in figure 13 of an area of nummular eczema. This can easily be distinguished from SJS clinically.

Columnist comments

The technique for doing a tissue aspirate for Gram’s stain and culture is as follows: Using a 22-gauge needle on a tuberculin syringe, into which about 0.2 ml of nonbacteriostatic sterile saline has been loaded. The subcutaneous area of maximum inflammation is aspirated as the needle is withdrawn. The saline IS NOT INJECTED, but rather used to assist in washing out the lumen of the needle directly onto some blood, chocolate and MacConkey agar, which is then processed in standard fashion.

In the February issue of Infectious Diseases in Children, I wrote an editorial regarding the response to the tsunami of last December 26 and contrasted the response in humanitarian aid to the tsunami victims with the lack of response to the daily tragedy of malaria, killing about 2,000 children per day. Well, I thought some recent good news, or at least encouraging news, was worth pointing out. Malaria was recently in the news again (June 10, 2005, issue of Science), as Dutch entomologists, Willem Takken and Bart Knols of the Wageningen University in the Netherlands, reported some success in controlling transmission of the infection by infecting the mosquito with a fungus, which inhibits its ability to take another blood meal by about 75%. This represents a small but significant step forward. A lot more could be done.

Lastly, as of this writing, the number of soldiers lost in the Iraq war is at 1,873 and in Afghanistan it is 228. By the way, there remain dozens of active duty pediatricians deployed, and make up one-third of deployed Medical Corps assessts, behind surgery and family medicine. Enough said.