Leyden: In the mid-1970s we were seeing lots of diaper rash at Children's Hospital in Philadelphia. I became convinced that there were two clinical variants. There was a severe type that I suspected was caused mainly by C albicans, and there was a more common type in which frictional forces seemed to be playing the major role. But, as you noted, the reigning theory in the literature then was that ammonia was the cause. When I looked for the source of that theory, I found it was traceable to one study done by Cooke in 1921.
Krafchik: She claimed the offending organism was Bacillus ammoniagenase. This has now been shown to be a Proteus organism.
Leyden: Yes. On the basis of one experiment, Dr. Cooke concluded that bacteria were breaking down or releasing ammonia from urea and that the ammonia caused the diaper dermatitis. In fact, children with and without diaper rash do harbor many organisms that can liberate ammonia from urea. We did studies of children with and without various forms of diaper rash and noted what kinds of organisms were present. We showed that if you measured the ammonia present in urine at the first diaper change in the morning, you couldn't show any difference in the concentration or amount of ammonia that was produced. We tried exposing scarified skin to urine with and without urease and at various pH levels. When we put ammonia on scarified skin, we saw only slight inflammation. We concluded that ammonia or urine itself was not the major cause of diaper dermatitis. The hypothesis we generated at that point was that the majority of diaper rash cases - other than the more severe ones involving C albicans - were due to frictional forces on wet skin rather than to ammonia. There had been studies suggesting that wet skin was more vulnerable to friction; we did similar experiments and got similar results. Berg and coworkers subsequently confirmed our results.
Krafchik: I may be old-fashioned, but I still suspect ammonia makes the rash worse, despite your findings. When we used to see babies with diaper dermatitis, we could always smell the ammonia.
Leyden: The nose is a tremendous detector. For some substances it beats gas chromatography-mass spectrometry. But the most we could show was that if you compromised the skin by scarification, you could get only a bit more erythema with ammonia exposure. It just wasn't a significant factor.
Schuman: Yet we used to be advised to add vinegar to the wash water when we washed cloth diapers - to lower the pH and counteract the ammonia.
Leyden: That's right. But probably if anything was important about washing cloth diapers, it was that they needed to be rinsed thoroughly so that there was no residual detergent on the surface that would then get onto the infant's skin and irritate it. In the cloth diaper era, that probably was very common.
Spraker: But weren't there other contributing factors? You mentioned pH, for example.
Leyden: There was general agreement back then that keeping urine acidified seemed to reduce irritation. As a result, cranberry juice and various ointments were rubbed on the skin to keep it more acidic. Buckingham and coworkers later demonstrated that, especially at an alkaline pH, a variety of proteases found in feces were capable of inducing irritation in a variety of experimental systems. So the pH of the urine with its effect on fecal proteases was recognized as another factor in the pathophysiology of diaper dermatitis. Still another factor that has not been well studied is the possible role of miliaria - failure to deliver sweat effectively to the skin surface. We demonstrated that, under occlusive dressings, plugs can develop in the acral portion of the sweat ducts and that certain organisms, particularly staphylococci, produce an extracellular polysaccharide-like substance that might be responsible.
Spraker: The mildest diaper dermatitis we see takes the form of small erythematous macules or papules.
Leyden: I think that's miliaria - prickly heat.
Spraker: And it goes away without any specific treatment.
Krafchik: These explanations sound very plausible. But all babies experience wetness and presumably friction. So why do some get dermatitis while the others don't?
Leyden: One reason is that the stratum corneum varies a lot from one baby to another. We and others have shown that if you hydrate skin repeatedly and apply a standardized frictional force, after a certain amount of time the skin will begin to get red and eventually break down. The time needed to produce that effect varies greatly from one baby to another, because the stratum corneum varies enormously in thickness and integrity. Before superabsorbent disposable diapers were available, the skin of babies was repeatedly hydrated and essentially encased in the equivalent of a plastic bag. The diaper area was extremely humid, and the skin remained moist. The problem would vary according to the chubbiness of the baby, how much the baby was moving, and whether the caregiver was washing it too frequently or too abrasively. Hydrated skin is more easily abraded. That's why one licks a finger to turn pages - the skin moisture increases friction. All of those factors contribute to making the baby's skin redden and on occasion become severely inflamed.
Spraker: What about other factors contributing to dermatitis - or to its decrease? What else besides the use of disposable diapers could explain the drop in incidence?
Schuman: Some studies have shown an association between breastfeeding and the incidence of diaper dermatitis, probably through some immunologic effect.
Leyden: Breastfeeding may alter the pH of the infant's feces to make them more acidic, and that could reduce the risk of dermatitis.
Spraker: So, in addition to the use of antibiotics, which encourages the growth of Candida, other secondary factors that can cause diaper dermatitis are frequency of changing, especially if there's a delay after fecal soiling, and breastfeeding or - rather lack of breastfeeding. What about diarrhea?
Leyden: Diarrhea certainly is not good. That would create another initiating factor.
Spraker: And the diarrhea associated with an illness may be different from normal stools. It may have a different pH and enzymatic activity.