I have several dermatological ailments and fortunately a
very good clinic of dermatologists. The
main problems have been atopic dermatitis (eczema) that did not start until I
was 65 and rosacea starting slightly later.
I have posts
on the pathophysiology of these conditions at the links. I have the predisposing factors including
genetics, ethnicity (fair-skinned individuals of Celtic and northern European
heritage (Fitzpatrick skin types I–II), and associated conditions (childhood
and adult allergic asthma) but did not get the associated atopic dermatitis at
the time. One of my siblings had both in
childhood. My father probably had
rosacea but he lived during a time when dermatology treatment was generally not
done by dermatologists and quite primitive. By primitive I mean, physicians
tried to excise inflammatory areas from his face instead of treating them
medically like they do now.
The global prevalence of rosacea is estimated at 5.46%
(4). Women are affected more than men
and peak prevalence occurs in middle age (45-60 years old). In a study that looked at how many people
were untreated – the prevalence was 12.3% in Germany and 5% in Russia. Nearly half of those affected had not
received any care in the previous year despite 1/3 endorsing a significant
effect on quality of life (5). In
addition to cosmetic effects rosacea is a cause of dry eyes and other
significant ocular complications and sensitive skin lowering the threshold for
pain and irritation.
I was doing quite well until I needed a change in sleep
apnea treatment. Three months ago I
changed from APAP to BiPAP because of an increasing AHI. Because it was running at much higher
pressure, they suggested using a mask rather than nasal CPAP. That mask led to a flareup of rosacea that
required a month of treatment with doxycycline.
But even after that treatment I was left with a 4-5 mm inflammatory
nodule beneath my right eye that did not resolve.
I saw a new dermatologist today and the conversation went
something like this:
Me: “This started
about 3 months ago when I tried a CPAP mask and it caused a flare-up of
rosacea. This nodular area did not clear
with doxycycline. At about 2 weeks the
area of inflammation extended up into the orbital area but stopped there ever
since.
Derm: “Are you still
using the triple cream?”
Me: “Yes twice a
day. It generally works great.”
Derm: Inspects the
area with a dermatoscope in detail and then: ’Yes, it looks like
inflammation. There may be some
microabscesses in the area. It does not
look like cancer or infection. What we
need to do is try a different antibiotic for a month and then if it doesn’t
clear up – do a biopsy. I am going to
prescribe cefuroxime after we make sure there are no drug interactions. I notice you are on flecainide. We were told never to prescribe it so I want
to make sure it does not interact.”
His scribe ran a drug interaction check. I set up an
appointment to see him in a month and picked up the prescription for
cefuroxime. On the way to the pharmacy,
I recalled enrolling patients in a cefuroxime trial for urinary tract
infections. And then I tried to recall
all of the serious side effects of cephalosporins – the class of antibiotics
that cefuroxime is in. That is just the
way my mind works.
What are the lessons about psychiatry here? I don’t think the lessons are for
psychiatrists because we know better.
The lessons are basically to counter all of the misinformation about
psychiatric treatment and medications from antipsychiatrists, health and
wellness influencers, and other critics who don’t seem to know very much about
the field. Here goes:
1: Diagnoses
are not easy – and experts are more likely to make them and even then
most are provisional. In all my teaching
about diagnostic thinking in medicine pattern matching is a significant
component. Dermatologists and
ophthalmologists are the examples I typically used comparing their diagnoses to
other physicians. In this case, the question is what any other physician would
have diagnosed the mark on my face as and how it would have been treated. I have actually been there and done that and
it would vary from no diagnosis or treatment to acne and metronidazole.
2:
Transdiagnostic – yes probably – you would think the term had
been invented for psychiatry in the last 10 years. It is typically used as a criticism of
categorical diagnosis as in “there are just so many transdiagnostic symptoms
nothing is specific?” And "all of this comorbidity is a strike against categorical diagnoses." The reality is
there are many so-called transdiagnostic symptoms across all of medicine and
many of them are more robust than psychiatric symptoms. Rash is one of the more robust. Rashes are transdiagnostic across the 2,000
to 3,000 conditions that produce similar rashes across disorders as well as within the same
category. There are many different
rashes (intermediate phenotypes) presenting as rosacea for example, in this
case a solitary inflammatory papule.
3: No labs? There is no lab test for rosacea or most
dermatology conditions. They are clinical diagnoses made on that basis
considering all of the findings at the time of the exam.
4: Is there a
biopsy result specific for rosacea?
This is a familiar criticism of psychiatric diagnoses – there is no specific
test that rules in the diagnosis. From reference 1 below: “A skin-biopsy
specimen is obtained only to rule out other diagnoses, since the
histopathological features of rosacea are typically not specific to rosacea.” Rosacea is a clinical diagnosis based on
history and phenotypic criteria and no specific diagnostic test is needed to
confirm it (3).
4: Prevalence
and Quality of Life Considerations – prevalence and quality of life
considerations for rosacea and common psychiatric disorders are similar.
Rosacea studies looked at pooled prevalence (5.46%) and
geographic prevalence (Germany 2.1–12.3%, Russia 5.0%, U.K. incidence rate 1.65
per 1,000 person-years (the only study to quantify incidence) rather than
interval prevalence (4-6). Rosacea is
not reported in the same intervals as psychiatric disorders because it is considered
a chronic relapsing condition even though a segment of these specific
psychiatric disorders has that same property. There is no cure - another frequent criticism of psychiatric diagnoses.
Although dermatology and psychiatry use different quality of
life (QoL) impairment scales, in the respective disorders about 11% of rosacea
patients report severe impairment and anxiety and depressive disorders report
ranges of 26-85% using a cut-off of 2 standard deviations over average community
ratings (7). There are also comorbidity
considerations with high percentages of rosacea patients reporting significant levels
of depression and anxiety.
5: Under and
missed diagnoses – deference to expert diagnosis is a time-honored tradition
in medicine with a more recently established empirical basis. Overall
diagnostic accuracy for dermatology conditions is 37-57%. Roughly ½ of these conditions are incorrectly
diagnosed in primary care compared with dermatologists (8). That rate of misdiagnoses
is similar to the rate for anxiety and depressive disorders in primary care of
40-50% (9-11).
6: Under
treatment – undertreatment follows underdiagnosis in most cases, but
undertreatment can also occur when the diagnosis has been established. In the case of rosacea delayed diagnosis can
lead to progressive (granulomatous) disease and ocular complications. Seborrheic
dermatitis is also a frequently co-occurring condition and patients are often
unaware that they have this condition as well.
Not treating depression and anxiety on a timely basis leads
to similar chronicity and conditions more resistant to treatment. It increases both the risk of suicide and self
harm with chronicity. Untreated depression and anxiety are risk factors for cardiovascular
disease and substance use. Chronic pain can be increased. Both conditions are well documented causes of
significant disability.
7: Uncertain pathophysiology – The pathophysiology of most psychiatric disorders where the possible cause has been ruled out is not known. The same is true for rosacea. In any similar group of medical disorders there are commonly suggested hypotheses that can be grouped by general mechanism as indicated in the table below:
8: Uncertain
medication mechanism of action/placebo response - Since the underlying pathophysiological is unknown
the mechanisms of action of the recommended treatments is unknown for rosacea
and psychiatric disorders. This means
that clinical trials are needed to test the efficacy and safety of treatments
and clinical care follows.
Comparisons of response rates in a selection of
antidepressant and rosacea medication trials show significant placebo response
in both with a slightly higher response rate in the rosacea trials (66% v.
50%). At the same time the metrics used for
effect size in both tables are not comparable.
If we change to a comparable metric like Number Needed to Treat (NNT) we
see ranges of 3-8 for rosacea and 4-6 for antidepressants. On that basis it is fair to say that response
rates to rosacea medication and antidepressants are generally comparable.
The strict comparison is limited by the fact that studies
have different outcome measures. Rosacea
studies use a clinician rated global improvement score. Antidepressant trials may also have a global improvement
score but more likely use clinical scales like the HAM-D or MADRS. Both types of ratings have a consensus marker
for improvement but they are not calibrated against one another. The placebo response rates may have different
mechanisms. Both may have a regression
to the mean and clinical care/therapeutic alliance component but the rosacea
trials can also be affected by atmospheric conditions and additional topicals that
can affect skin moisture. Rosacea trials
tend to be longer than antidepressant trials (12-16 weeks versus 8-12 weeks).
There is a question of real-world effectiveness with both
conditions. It has been studied in
depression (12). It was found that for MDD, there is a 90% gap between those
with the diagnosis and this receiving effective treatment (41.8% receive treatment
and of those only 23.2% of those diagnosed received effective treatment.) The RISE study (5) suggests that in a
screened population for rosacea, 80% were never previously diagnosed. Of the 20% who
were 47.5% had received no rosacea care whatsoever, and
only 23.7% had received topical and/or systemic drugs suggesting
similar underdiagnosis and treatment as depression.
Whenever clinical trials of antidepressant are discussed, some critics say that the lack of hard outcomes (all-cause mortality, cause-specific mortality (MI, stroke, suicide), hospitalization) as opposed to symptom-based outcomes is a major problem. In the comparison with rosacea – all of the outcome measures are symptom-based and no evidence that treatment prevents associated or long-term complications like rhinophyma, telangiectasia, or ocular complications. There are register based/naturalistic studies (outside of clinical trial design) that show long term use of antidepressants reduces all cause mortality, suicidal ideation, and cardiovascular mortality (13-17). Not all analyses agree and in some cases the argument was made that it was an antidepressant class effect (18,19). Rosacea on the other hand has not been studied against an all cause mortality endpoint because it is not associated with increased mortality.
9: On label - off-label - There are currently 40 FDA approved medication for depression and 10 FDA approved medications for rosacea. Antidepressant development dates back to the 1950s when it was discovered that medications used to treat tuberculosis also had positive effects on mood. Rosacea medication development began as an early topical antibiotic treatment (Sodium sulfacetamide 10%/sulfur 5% for papules/pustules). That early treatment was before 1962. The next development did not occur until topical metronidazole in 1988. The only oral antibiotic approved is doxycycline 40 mg MR (Oracea) that is a combination of doxycycline 30 mg IR and doxycycline 10 mg delayed release (DR). There are no combination medications approved despite the fact that there are compounded formulations. As an example the Rosacea triple cream contains metronidazole, ivermectin, and azelaic acid. Each component is FDA approved for monotherapy.
10: Politicalization – the only real criticism
I have seen of dermatologists was comedic. In an episode of Seinfeld,
Jerry was trivializing what dermatologists do until he was reminded that they
diagnose and treat skin cancer. Despite
the parallels to psychiatry, they have no anti-factions or health and wellness
influencers suggesting they are creating more problems than they solve or negative
media coverage or high visibility criticism by experts in their own field. The head of HHS is not suggesting their treatments
are overprescribed.
There is no great agitation over dermatology – their methods
or treatments despite similar levels of uncertainty and clinical methods with
psychiatry. I am not suggesting there
should be. I am suggesting that
psychiatry should be approached by outsiders with the same levels of acceptance
that they have for dermatology. I am
also suggesting that if you have a skin condition and nobody seems to be able
to diagnose or treat it – see a dermatologist. The advice applies to a mental
disorder. See an expert in that
field.
I know this does happen but there is always a delay. And there is always plenty of misinformation about the field. As I have posted here before – practically all of the people I saw over my 40-year career had seen somebody else first – often many different people over a number of years before they decided to see a psychiatrist. It was often the result of a referral decision. But most importantly – don’t believe what you read in the papers whether it is health and wellness advice or recommendations by the current Secretary of HHS.
If there is a serious problem with your mental
state – see the right person.
George Dawson, MD, DFAPA
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