| Starting in 1995 in North America Skin Cap became very popular among psoriatics because it was often helpful where other treatments,
including topical corticosteroids, had been ineffective. Dermatologists were very impressed with the results and with the
apparent safety, and many dermatologists recommended Skin Cap spray to their patients, and some sold Skin Cap spray to their
patients. Skin Cap spray was also sold by mail order, through 1-800 numbers, and at some pharmacy chains.
The story of Skin Cap unfolded for many dermatologists and for many patients on the internet, notably in the RxDerm-L mailing
list for dermatologists, and on the alt.support.psoriasis newsgroup for psoriatics. Those who monitored these sources of information
(and occasional misinformation and misplaced enthusiasm) were among the first to become aware of Skin Cap, and were also among
the first to become aware of potential problems with Skin Cap.
Dermatologists noted that Skin Cap appeared to be a very potent broad spectrum anti-inflammatory, and reports of Skin Cap's
effectiveness in the management of recalcitrant inflammatory diseases including discoid lupus, dermatomyositis, and lichen
planus were posted on the Internet mailing list RxDerm-L.
Apart from occasional reports of skin irritation after exposure to Skin Cap, or explosive flares of psoriasis when Skin Cap
was stopped, there were no reports of problems with Skin Cap.
In 1996 information started to circulate that some jurisdictions in Europe (notably Austria and Holland) had found corticosteroids
(clobetasol propionate or triamcinolone) in Skin Cap, and had banned Skin Cap for this reason.
In July 1997 samples of Skin Cap spray sold in North America were found by several excellent laboratories, including the Mayo
Clinic and Glaxo Inc. using "high performance liquid chromatography" to contain clobetasol propionate. This finding has been
disputed by Cheminova Inc., the marketer of Skin Cap. Cheminova had denied that there are corticosteroids in Skin Cap, and
Cheminova has asserted that when Skin Cap is analyzed using the MALDI-TOF mass spectrometer test it will show that Skin Cap
contains a chemical which is confused with - but is not the same as - clobetasol propionate on high performance liquid chromatography.
Regardless of how the issue of the presence or absence of corticosteroids in Skin Cap is resolved, this episode has served
to remind the dermatology community of a number of basic principles.
- We are responsible for the consequences of the advice we give our patients.
- Our patients see us as "learned intermediaries", and they expect us to assess the risks and benefits of therapies we suggest.
- There is a basic list of questions which applies, to a greater or lesser extent, to all proposed therapies. Even if not
all of the questions can be adequately answered for a given therapy, these questions serve as a useful screen for potential
problems and for issues which must be considered:
- What is the mechanism of action for the proposed therapy? "How does this stuff work?" When we consider the proposed mechanism
of action, it sometimes is possible to predict responses to therapy, potential risks, and beneficial or adverse interactions
with other forms of therapy.
- What chemicals are in this medicine, other than the active ingredient? Certain chemicals, for example ethanol or lactose
(to say nothing of clobetasol propionate!), can cause problems in some patients. For this reason complete disclosure of all
ingredients in a medication has been mandatory for the past 30 years in North America. The statement that there are "secret
ingredients" should raise the suspicion that the manufacturer is violating some law, or at least probably including something
a physician might find objectionable. As a practical matter, there are no prescription or non-prescription medicines (with
the notable exception of Skin Cap) sold in North America for which a complete list of all active and "inactive" ingredients
is not immediately available from the manufacturer.
- What problems have been found in animal studies on this product? The absence of data from animal studies should raise concern
that our patients may wind up playing the role that should have been reserved for experimental animals.
- Are there some patients (for example children, pregnant women, or old people) who should not use this medicine?
- Are there some parts of the body where this medicine should not be applied?
- Is there a safe limit to the duration of time for which this medicine should be used?
- Is there a safe limit to the amount of this medicine that can be used every day, or a limit to the total dose the patient
can be exposed to?
- Are there some patients who are at increased risk for complications, for example because of previous or current therapies
(eg. Radiotherapy or ultraviolet light treatment)?
- Are there some therapies which complement this treatment and perhaps reduce the risk of complications?
- What sort of monitoring and followup are needed in order to deliver safe treatment?
What did we learn from our experience with Skin Cap? We were reminded of all of the above points. When did we learn the things
listed above? We learned to ask these questions in basic pharmacology classes, in first or second year medical school. This
list of basic questions evolved over the past 150 years, as the medical profession and the pharmaceutical industry have developed
their ability to use pharmacologic agents in ways that create maximum benefit for patients with the smallest practical risk.
We have learned from hard experience, and sometimes at great cost to our patients, that generally therapies which are very
potent usually also can cause serious problems under some circumstances. It is fortunate (for our patients and for us) that
the distribution of Skin Cap -- apparently an extremely potent broad spectrum anti-inflammatory medication -- was stopped
before serious harm could result. When the above questions have been properly addressed Skin Cap (or a product similar to
it) may find an appropriate use in dermatology.
In our enthusiasm for a new and apparently effective therapy which helped some of our most desperate patients we forgot to
ask the questions we learned to ask early in medical school. When we failed to ask these questions -- when we failed to subject
Skin Cap to the same scrutiny that is routine for prescription medicines -- we failed to act in the manner of a "learned intermediary",
a vital role our patients expect us to play.
We also learned that the internet facilitates dissemination of clinical experience very efficiently, but without the safeguards
provided by peer reviewed journals. In a mailing list like RxDerm-L this lack of peer review is to some extent compensated
for by feedback from other members of the mailing list, and members of RxDerm had the advantage of being among the first dermatologists
to be exposed to negative comments and questions about Skin Cap.
KC Smith MD FRCPC
Editorial Comments should be considered
to represent the opinion of the author
and do not necessarily represent the
opinion of the Journal or the Regents
of the University of California.
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