Validation of Dermoscopy as a Real

STUDY
Validation of Dermoscopy as a Real-time
Noninvasive Diagnostic Imaging Technique
for Actinic Keratosis
Marı́a Huerta-Brogeras, MD, PhD; Olga Olmos, MD, PhD; Jesús Borbujo, MD, PhD;
Almudena Hernández-Núñez, MD, PhD; Esther Castaño, MD, PhD; Alberto Romero-Maté, MD;
Diego Martı́nez-Sánchez, MD; Cristina Martı́nez-Morán, MD
Objective: To validate dermoscopy as a real-time non-
invasive diagnostic imaging technique for actinic keratosis (AK).
Design: Prospective study to validate a diagnostic test.
Setting: Dermatology department of a tertiary university hospital in Fuenlabrada, Madrid, Spain.
Patients: A total of 178 patients with a clinical diagnosis of AK participated in the study.
ated. The concordance between dermoscopy results and
histopathological findings was 0.917. The sensitivity of
dermoscopy for the diagnosis of AK was 98.7%, with a
specificity of 95.0%, a positive likelihood ratio of 19.74,
and a negative likelihood ratio of 0.01. A diagnostic algorithm that combined follicular openings and erythematous pseudonetwork demonstrated a sensitivity of 95.6%
and a specificity of 95.0% for the diagnosis of AK.
Main Outcome Measures: An independent blinded
comparison was performed between dermoscopy results and histopathological findings, the gold standard
for the diagnosis of AK. All the patients underwent both
diagnostic tests.
Conclusions: The sensitivity and specificity of dermoscopy for the diagnosis of AK were high, as was the concordance between dermoscopy results and histopathological findings. As a real-time noninvasive diagnostic
imaging technique for AK, dermoscopy may be incorporated in the management of patients with these
lesions.
Results: One hundred seventy-eight lesions were evalu-
Arch Dermatol. 2012;148(10):1159-1164
A
Author Affiliations:
Department of Dermatology,
Fuenlabrada University
Hospital, Fuenlabrada
(Drs Huerta-Brogeras, Borbujo,
Hernández-Núñez, Castaño,
Romero-Maté,
Martı́nez-Sánchez, and
Martı́nez-Morán), and Jazmı́n
Health Center (Dr Olmos),
Madrid, Spain.
CTINIC KERATOSIS (AK) IS
defined as an in situ intraepidermal carcinoma or
precancerous disease that
occurs in areas of skin exposed to sunlight, characterized by the
presence of an abnormal proliferation and
differentiation of epidermal keratinocytes, with a risk for progression to infiltrating squamous cell carcinoma (SCC).
In the United States, AK represents the
third most frequent condition for which
dermatologic consultation is sought, accounting for 11.2% of visits.1 The risk for
transformation to SCC is 0.075% to
0.096% per AK lesion per year.2 This risk
is cumulative in patients with multiple AK
lesions and can reach 10% within 10 years
or up to 20% among immunocompromised patients or those who remain untreated.3 Squamous cell carcinoma is a
clinical, biological, and histopathological continuum of AK and is the principal
cause of death from nonmelanoma skin
cancer4-6; therefore, patients with AK are
ARCH DERMATOL/ VOL 148 (NO. 10), OCT 2012
1159
candidates for periodic follow-up dermatologic evaluation as outpatients.
Dermoscopy is a real-time noninvasive diagnostic imaging technique. For the
user, its optical system renders the corneal layer translucent to improve vision,
with original magnification ⫻10 to ⫻400.
The technique increases the diagnostic accuracy of clinical evaluation by the dermatologist. The aim of dermoscopy is to
overcome the imprecision and limits of
clinical diagnosis that are associated with
histopathological investigation, considered the gold standard technique by the
scientific community. The dermoscopic
signs of AK are erythematous pseudonetwork, surface scale, linear-wavy vessels,
and follicular openings.7-9 The overall dermoscopic pattern of AK is a “strawberry”
appearance. The primary objectives of the
present study were to validate dermoscopy as a real-time noninvasive diagnostic imaging technique for AK (based on the
presence of the strawberry pattern) and to
measure the sensitivity, specificity, posi-
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Author Affil
Department
Fuenlabrada
Hospital, Fu
(Drs HuertaHernández-N
Romero-Mat
Martı́nez-Sán
Martı́nez-Mo
Health Cente
Madrid, Spai
Table 1. Comparison of Dermoscopic and Histopathological
Diagnoses of Actinic Keratosis (AK) Among 178 Lesions a
Histopathological
Diagnosis
Dermoscopic
Diagnosis
Yes
No
Total No. (%)
Yes
No
Total
156
2
158
1
19
20
157 (88.2)
21 (11.8)
178 (100.0)
a Using histopathological findings as the gold standard test result, the
sensitivity of dermoscopy for the diagnosis of AK was 98.7%, and the
specificity was 95.0%. The proportion of false-positive results was 5.0%,
and the proportion of false-negative results was 1.3%.
tive and negative likelihood ratios, and positive and negative predictive values compared with the gold standard
of histopathological studies. Secondary objectives were
the following: (1) to evaluate which of 4 dermoscopic
signs was most sensitive and specific for AK, measuring
the association between each dermoscopic sign and the
histopathological diagnosis; (2) to describe new dermoscopic criteria (if detected) for the diagnosis of AK;
(3) to assess the correlations or associations among the
4 dermoscopic signs that mimic the strawberry pattern
of AK; (4) to determine the dermoscopic sign or combination of signs with the highest sensitivity and specificity for the diagnosis of AK; and (5) to study the relationship between the dermoscopic signs of AK and
epidemiological data.
METHODS
This prospective study was conducted in the Department of Dermatology, Fuenlabrada University Hospital, Madrid, Spain, during a 12-month period from June 1, 2006, through May 31, 2007.
The study inclusion criterion was clinical suspicion of AK (ie,
erythematous plaque with surface scale in an area of skin exposed to sunlight). Inclusion was not limited by the size of the
lesions or by their clinical forms (ie, atrophic vs hypertrophic
or pigmented vs nonpigmented). The study exclusion criteria
were the following: pregnancy or breastfeeding, associated conditions that were contraindications to the use of local anesthesia to perform biopsy, and clinical suspicion of skin cancer melanoma or nonmelanoma (signs of infiltration, marked
hyperkeratosis, or the presence of a hemorrhagic crust or bleeding). The ethics committee of Severo Ochoa Hospital, Madrid,
Spain, evaluated and approved the research project. Informed
consent was obtained from all study patients in accord with the
principles of the Declaration of Helsinki. For a CI of 95% and
a statistical power of 80%, calculation of the sample size for
studies of diagnostic tests indicated that the estimated sample
should comprise 172 analysis units (in this case, AK lesions).
Only 1 lesion was studied in each patient. At the time of their
inclusion in the study, all the patients underwent dermoscopy
and histopathological investigation. Dermoscopic photographs were taken using a dermoscope (FOTO; DermLite) attached to a camera (400D; Canon). Histopathological investigation was performed on a punch biopsy specimen. An
independent blinded comparison was performed between dermoscopy results and histopathological findings. To avoid bias
because of revision of the diagnosis, an expert dermoscopist
among us (M.H.B.) was blinded to the histopathological diagnosis; to avoid bias in the histopathological analysis, the pa-
thologist who reviewed the specimen was blinded to the dermoscopic diagnosis.
In this series, dermoscopic diagnosis of AK was established
by the presence of 2 or more of the following 4 dermoscopic
signs: (1) erythematous pseudonetwork (pink erythematous
base that is interrupted by the prominent follicular or adnexal
openings), (2) surface scale (homogeneous areas or structures
of yellow-white or brown), (3) linear-wavy vessels (fine,
curved, wavy vessels around the white halo at the orifices of
the hair follicles), and (4) follicular openings (yellow ovoid or
globular structures with a white halo, forming a target image).
Negative dermoscopic diagnosis of AK was based on the absence of at least 3 of 4 dermoscopic signs and the presence of
criteria suggestive of other diagnoses, in particular the following vascular patterns: glomerular vessels in SCC, crown vessels in sebaceous hyperplasia, and arboriform telangiectasias
in basal cell carcinoma. Dermoscopic images for each lesion
were evaluated by the same observer (M.H.B.) at all the end
points during the study period to confirm reproducibility of
the results. In addition, the age, sex, skin phototype, and site
of the lesion were recorded for each patient. In the histopathological study, the presence or absence of epidermal dysplasia was determined.
Statistical analysis was performed on data from lesions seen
in the department that manifested clinical signs of AK. Sensitivity and specificity were determined for dermoscopic diagnosis and for each dermoscopic variable compared with routine histopathological studies as the reference, and P values were
calculated using the ␹2 tests. Nonparametric correlation (Pearson product moment ␹2 test) was used to determine the association between individual dermoscopic variables. The concordance between dermoscopy results and histopathological
findings was determined by calculating the ␬ value. All the data
analyses were conducted using available software (SPSS for Windows version 12.0; SPSS Inc). For categorization purposes, classification and regression tree software (CART 4.0; Salford Systems) was used. In the latter analysis, classification trees were
applied to learning sets to search for optimal split variables.
RESULTS
In total, 178 lesions on 178 patients were clinically considered AK. All the patients agreed to participate in the
study and signed the consent form. One hundred fifteen
lesions (64.6%) were observed in men, and 63 lesions
(35.4%) were observed in women. Patient age ranged from
37 to 97 years (mean age, 67 years). The most frequent
sites of the lesions were the face (139 lesions [78.1%])
and the scalp (36 lesions [20.2%]); the remainder were
on the back or the upper extremities.
Most patients (144 patients) had skin phototype II.
The remaining patients had skin phototype III (28 patients) or skin phototype I (6 patients).
The dermoscopic diagnoses and histopathological diagnoses for 178 lesions are summarized in Table 1 and
Figure 1. The histopathological types of AK were not
recorded because such determination was excluded from
the pathologist’s usual practice for biopsy specimens of
these lesions. Furthermore, the pathologist was blinded
to the dermoscopic diagnosis.
Using histopathological findings as the gold standard test result, the sensitivity of dermoscopy for the diagnosis of AK was 98.7%, and the specificity was 95.0%.
The proportion of false-positive results was 5.0%, and the
proportion of false-negative results was 1.3%. The posi-
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178 Lesions clinically suspicious of AK
178 Lesions included in the study
178 Biopsy and histopathological study
178 Dermoscopic study of signs (erythematous
pseudonetwork, linear-wavy vessels,
surface scale, follicular openings)
Presence of ≥2 signs
Presence 0-1 sign
157 Dermoscopic diagnosis
of AK
21 Dermoscopic diagnosis
of “not AK”
1 False positive
Dermoscopic diagnosis
of AK
Histopathological
diagnosis of SL
2 False negatives
Dermoscopic diagnosis
of SK, SL
Histopathological
diagnosis of AK
20 Histological diagnosis of
“not AK”
7 Squamous cell carcinoma
6 Basal cell carcinoma
3 SK
2 Solar lentigo
1 Lichenoid keratosis
1 Sebaceous hyperplasia
158 Histopathological diagnosis
of AK
Figure 1. Flowsheet of patients in the study. AK indicates actinic keratosis; SK, seborrheic keratosis; and SL, solar lentigo.
Table 2. Sensitivity, Specificity, ␬ Index, and Positive and Negative Likelihood Ratios Among 4 Dermoscopic Signs
of Actinic Keratosis
Sensitivity
Specificity
␬ Index
Positive
Likelihood
Ratio
116/158 (73.4) [66.2-80.6]
148/158 (93.7) [89.6-97.8]
104/158 (65.8) [58.1-73.5]
136/158 (86.1) [80.4-91.8]
20/20 (100.0) [97.5-100.0]
7/20 (35.0) [11.6-58.4]
19/20 (95.0) [83.0-100.0]
19/20 (95.0) [83.0-100.0]
0.383
0.307
0.282
0.556
Infinity
1.44
13.16
17.22
No./Total No. (%) [95% CI]
Dermoscopic Sign
Erythematous pseudonetwork
Surface scale
Linear-wavy vessels
Follicular openings
tive predictive value was 99.4%, and the negative predictive value was 90.5%. The concordance between dermoscopic results and histopathological findings, calculated
using the ␬ statistic, was 0.917. Dermoscopic diagnosis
of AK had a positive likelihood ratio of 19.74 and a negative likelihood ratio of 0.01. The 4 dermoscopic signs of
AK are listed in Table 2, along with their individual sensitivities, specificities, ␬ indexes, and positive and negative likelihood ratios. Classification trees were used for
the descriptive analysis, seeking the combination of dermoscopic signs that best predicted the histopathological results. A diagnostic algorithm that combined follicular openings and erythematous pseudonetwork
demonstrated a sensitivity of 95.6% and a specificity of
95.0% for the diagnosis of AK.
Analysis of the correlation among the 4 dermoscopic
signs using the Pearson product moment ␹2 test revealed significant associations (P⬍.05) for surface scale,
linear-wavy vessels, and follicular openings (Table 3).
Analysis of the correlations between the dermoscopic signs
and epidemiological data revealed the following 2 statistically significant findings (P⬍ .05): linear-wavy vessels were more common in men, and follicular openings
were less common in patients younger than 50 years
(about 40% vs a mean of almost 80% in other age groups).
In this series, 4 of 7 SCCs diagnosed based on histo-
Negative
Likelihood
Ratio
0.27
0.18
0.36
0.15
pathological findings had a vascular pattern suggestive
of SCC on dermoscopy, while the only dermoscopic sign
observed in 2 of these cases was hyperkeratotic surface
scale.
COMMENT
The present study validated dermoscopy used on lesions selected by visual inspection as a real-time noninvasive diagnostic imaging technique for AK by comparing dermoscopy results with histopathological findings,
achieving a sensitivity of 98.7% and a specificity of 95.0%.
The concordance (␬ index) between dermoscopy results and histopathological findings was 0.917. Based on
considerations by the Evidence-Based Medicine Working Group,10 the positive and negative likelihood ratios
(19.74 and 0.01, respectively, in this series) are clinically relevant to the interpretation of results because they
respectively reflect increased and decreased likelihood
that a diagnosis may or may not be accurate in a significant manner with respect to not performing a diagnostic test.
The aim of this study was to validate dermoscopic criteria for AK. The features most consistently found on dermoscopy were follicular openings and erythematous pseu-
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Table 3. Results of the Pearson Product Moment ␹2 Test to Determine Correlations Among 4 Dermoscopic Signs of Actinic Keratosis
Variable
Erythematous pseudonetwork
␹12 statistic
P value
Surface scale
␹12 statistic
P value
Linear-wavy vessels
␹12 statistic
P value
Follicular openings
␹12 statistic
P value
Erythematous Pseudonetwork
Surface Scale
Linear-Wavy
Vessels
Follicular Openings
...
...
2.7
.10
3.2
.08
19.2
⬍.001
2.7
.10
...
...
6.8
.009
3.5
.06
3.2
.08
6.8
.009
...
...
11.1
.001
19.2
⬍.001
3.5
.06
11.1
.001
...
...
Abbreviation: Ellipsis, not applicable.
A
B
C
D
Figure 2. Dermoscopic signs of actinic keratosis. A, Follicular openings with keratotic plugs (arrows). B, Erythematous pseudonetwork. C, Surface scale.
D, Linear-wavy vessels surrounding hair follicles (arrows).
donetwork. Follicular openings (Figure 2A) showed the
highest concordance with the histopathological diagnosis (␬ index, 0.556). This dermoscopic sign had more balanced values of sensitivity and specificity. Erythematous pseudonetwork (Figure 2B) was the most specific
of 4 dermoscopic signs evaluated. On dermoscopy, the
normal superficial vascular plexus is seen as a regular
blurred network of wide vessels. When AK forms, edema
and elastosis develop, producing a dermoscopic pattern
of erythematous pseudonetwork. One of the characteristics of aging skin is a loss of the vascular bed, and most
AK lesions are observed in older individuals. The vessels in AK may be present in the most atrophic areas of
the epidermis and dermis, around the orifices of the adnexa and follicles. The combination of dermoscopic signs
was sought that provided the highest diagnostic accuracy using classification trees. According to this descriptive method, the results herein demonstrate that the diagnosis of AK could be based on the combination of
follicular openings and erythematous pseudonetwork,
with a sensitivity of 95.6%, a specificity of 95.0%, and a
␬ index of 0.801). The diagnostic accuracy of this com-
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bination could be considered equivalent to that of the
strawberry pattern observed by Zalaudek et al.8 Surface
scale (Figure 2C) was the most sensitive dermoscopic sign
but had the lowest specificity and the lowest positive predictive value. This dermoscopic sign has been reported
in other neoplastic diseases such as Bowen disease11 and
lichenoid keratosis, as well as in certain inflammatory skin
lesions such as psoriasis. Linear-wavy vessels (Figure 2D)
represent a highly specific (95.0%) but not particularly
sensitive (65.8%) dermoscopic sign.
The dermoscopic vascular pattern is considered more
relevant in nonpigmented skin lesions12 such as AK. Proof
of this in the present study is the high positive predictive value (99.0%) for the presence of these characteristic vessels. Assessment of the possible relationships across
dermoscopic criteria showed that the vascular pattern was
associated with surface scale and with follicular openings. The presence of erythematous pseudonetwork
showed a statistically significant correlation with the presence of follicular openings. This association is logical given
the origin of erythematous pseudonetwork, described in
the previous paragraph. An evaluation was also performed of the relationship between the dermoscopic signs
of AK and epidemiological data. Statistically significant
associations were found with 2 dermoscopic signs: linearwavy vessels were more common in men, and follicular
openings were less common in patients younger than 50
years. The dermis underlying an AK lesion manifests actinic elastosis and vascular ectasia, correlating with the
vascular structures visualized on dermoscopy. In this series, actinic elastosis was significantly more common in
men than in women, a finding that may be explained by
greater occupational exposure to sunlight among men.
The fact that follicular openings were more common in
older patients may be explained by the aging of the skin,
which leads to approximately a 23% reduction13 in sebum production per decade, with greater cutaneous xerosis and more compaction of the stratum corneum.
Dermoscopy may be a promising technique for noninvasive detection of AK, perhaps overcoming the imprecision and limits of clinical diagnosis that are associated with histopathological investigation. Among
various studies,14-18 the positive predictive value for
clinical diagnosis has ranged between 74% and 81%. In
this study, clinical diagnosis and dermoscopic diagnosis achieved positive predictive values of 88.7% and
99.4%, respectively. Notably, these values are higher
than those reported for reflectance confocal microscopy, which is a noninvasive diagnostic tool with results closely linked to histopathological findings.19-21
Actinic keratosis may be considered a precursor of
SCC.22 The authors of a retrospective study23 proposed
a progressive dermoscopic model in which AK develops
into intraepidermal carcinoma and invasive SCC. The
present study extends their results by providing the
sensitivity and specificity for 2 of their evaluated criteria, namely, erythematous pseudonetwork and follicular openings. According to their findings, a red erythematous pseudonetwork was seldom seen in
intraepidermal carcinoma or invasive SCC, and it was
the most specific feature associated with AK. Those authors found that the presence of dotted or glomerular
vessels and discrete yellow-white opaque scales was significantly associated with intraepidermal carcinoma,
while the present study found surface scales to be the
least specific among 4 dermoscopic signs of AK.
Limitations of the present study include that no anatomicoclinical classification of AK (eg, atrophic vs hypertrophic or pigmented vs nonpigmented) was performed. Correlations between the dermoscopic criteria
and the histopathological and clinical types of AK could
be a subject for future studies. As with most diagnostic
techniques in the health sciences, correct dermoscopic
technique requires training. The dermoscopy herein was
performed by a dermatologist with considerable experience in dermoscopy. Future studies will be designed to
determine interobserver variability in the technique.
The findings of the present study have major practical applications in the field of skin cancer. The use of dermoscopy is described for the diagnosis of AK; this noninvasive technique can be performed in the office as part
of daily clinical practice and provides immediate results, with consequent prognostic and therapeutic implications. Because dermoscopy is not a costly technique, its use is important not only for the individual
patient and physician but also for the health system in
general. Dermoscopy may be incorporated as a noninvasive strategy for the diagnosis of AK and in the management of patients with these lesions.
Accepted for Publication: March 10, 2012.
Correspondence: Marı́a Huerta-Brogeras, MD, PhD, Department of Dermatology, Fuenlabrada University Hospital, 2 Camino del Molino, 28942 Fuenlabrada, Madrid, Spain ([email protected]).
Author Contributions: Drs Huerta-Brogeras, Olmos, Borbujo, Hernández-Núñez, Castaño, Romero-Maté, Martı́nez-Sánchez, and Martı́nez-Morán had full access to all
the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Huerta-Brogeras, Olmos, and
Borbujo. Acquisition of data: Huerta-Brogeras, HernándezNúñez, Castaño, Romero-Maté, Martı́nez-Sánchez, and
Martı́nez-Morán. Analysis and interpretation of data:
Huerta-Brogeras, Borbujo, and Martı́nez-Sánchez. Drafting of the manuscript: Huerta-Brogeras, Castaño, RomeroMaté, Martı́nez-Sánchez, and Martı́nez-Morán. Critical
revision of the manuscript for important intellectual content: Huerta-Brogeras, Olmos, Borbujo, HernándezNúñez, Castaño, and Romero-Maté. Statistical analysis:
Huerta-Brogeras, Olmos, and Borbujo. Obtained funding: Huerta-Brogeras. Administrative, technical, and material support: Huerta-Brogeras and Martı́nez-Morán. Study
supervision: Huerta-Brogeras, Olmos, Borbujo, HernándezNúñez, Castaño, and Romero-Maté.
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by
a grant PI 07/00735 from the Carlos III Health Institute
Research Fund for Research in Health Technology and
by grant BE67392009 from the Mutua Madrileña Foundation for Medical Research. These grants were from public funds.
Role of the Sponsor: The sponsors had no role in the design or conduct of the study; in the collection, analysis,
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or interpretation of the data; or in the preparation, review, or approval of the manuscript.
Additional Contributions: Jesús Juan Ruiz, PhD, provided advice on the statistical analysis.
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18. Whited JD, Horner RD, Hall RP, Simel DL. The influence of history on interobserver
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19. Horn M, Gerger A, Ahlgrimm-Siess V, et al. Discrimination of actinic keratoses
from normal skin with reflectance mode confocal microscopy. Dermatol Surg.
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Notable Notes
Beauty Tips From Ancient Queens
The quest for beauty stretches back into antiquity. Here are
some favorite beauty recipes from queens of yesteryear.
Poppaea Sabina (30-65 CE) was the second wife of the Roman Emperor Nero. She spared no effort to maintain her beauty,
bathing regularly in donkey’s milk.1 Poppaea kept on hand many
lactating she-donkeys to supply the necessary bath milk. According to the Roman author Pliny the Elder, donkey’s milk
was thought to eliminate facial wrinkles and keep the skin
smooth and delicate, while preserving its whiteness.1 Unrefrigerated milk, such as used by Poppaea, naturally sours to
produce lactic acid, an ␣-hydroxy acid, which has exfoliant properties. Perhaps Poppaea’s skin benefited from such lactic acid
production, assuming that it formed in her milk bath.
Jezebel was a wicked queen of Israel who reigned during
the ninth century BCE, until a rebellion against the monarchy developed. Leading the insurrection was Jehu, a newly
anointed king, who was ordered to exact retribution against
Jezebel. Knowing what danger she was in, Jezebel adorned
herself with an eye paint, biblically termed Puch (II Kings 9:30),
hoping to seduce Jehu and thereby save her life. Puch was an
eye cosmetic that when applied to the lids and lashes gave
the illusion of enlarging the eyes. The exact identity of Puch
is not known, although it has been suggested that it might
have contained antimony sulfide, which was used as an eye
cosmetic in ancient Egypt, along with lead-based compounds.2 Jehu was unimpressed by Jezebel’s appearance and
had her thrown from the palace window and killed.
In ancient Persia, some 2500 years ago, all eligible women
were forced to participate in a beauty contest, with the winner becoming the queen for a king named Achasverosh. According to the Bible (Esther 2:12), the women underwent
6 months of anointing with “oil of myrrh.” Oil of myrrh probably was unripe olive oil prepared with myrrh (Commiphora
myrrha).3 This cosmetic caused the skin to glow and had a
depilatory function. Today, myrrh is used as a fragrance in
cosmetics, and olive oil is used as a skin moisturizer with possible medical benefits.4 The beauty contest winner was Esther, who was Jewish. She was beautiful but also had great
charm owing to her modesty and virtue. As queen, Esther
helped to save the Persian Jews from annihilation as commemorated by the holiday of Purim.
Human nature being what it is, the ancient quest for beauty
goes on. There is nothing wrong with trying to be attractive,
as long as we remember that good looks often fade with time
and thus do not determine an individual’s worth. Rather, true
lasting beauty is found in the nobility of a person’s character
and in the degree to which someone is guided by human and
spiritual values.
Leonard J. Hoenig, MD
Contact Dr Hoenig at 601 N Flamingo Rd, Ste 201, Pembroke Pines, FL 33028 ([email protected]).
1.
2.
3.
4.
Turner P, ed. The Natural History of Pliny. Holland P, trans. New York, NY: McGraw-Hill; 1964:284-285.
Preuss J, ed. Biblical and Talmudic Medicine. Rosner F, trans-ed. Northvale, NJ: Jason Aranson Inc; 1993:280.
The Torah: With Ramban’s Commentary Translated, Annotated, and Elucidated. Brooklyn, NY: Mesorah Publications Ltd; 2009(4):349.
Baumann L, Woolery-Lloyd H, Friedman A. “Natural” ingredients in cosmetic dermatology. J Drugs Dermatol. 2009;8(6)(suppl):s5-s9.
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