10.5826/dpc.1201a31
Introduction: Actinic keratosis (AK) is a known indicator for sun damage, and subsequent squamous cell cancer may develop. The actinic keratosis and severity index (AKASI) is a recently developed tool that can evaluate both field cancerization and AK severity.
Objectives: We sought to evaluate if AKASI was a good predictor of cancer in AK patients and to compare AKASI with both the Physician Global Assessment (PGA) and total lesion count (TLC).
Methods:  Ninety patients with AK were included in the study. Each patient was examined, and AKs were scored with AKASI, PGA and TLC by 2 dermatologists. The AKASI, PGA and TLC values were compared between patients with skin cancer and patients without skin cancer.
Results: Mean AKASI, PGA, and TLC scores were 4.9, 1.7 and 9 respectively. The patients with skin cancer had higher scores of AKASI, PGA and TLC compared to the patients without skin cancer (P = 0.022, P = 0.014, P = 0.005, respectively). AKASI, PGA and TLC were very strongly correlated with each other (P &lt; 0.001). The AKASI threshold value for NMSC was determined to be 5.1.
Conclusions: AKASI, PGA and TLC may be used in the assessment of the severity of AK in daily practice or studies and may be considered as valuable tools in determining high-risk patients and to choose treatment option. AKASI seems to have an advantage to give a numeric threshold value for skin cancer.
text/xml
2160-9381
1838
en
Isil Karaarslan
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
total lesion count
Comparison of Actinic Keratosis and Severity Index with Physician Global Assessment and Total Lesion Count and the Ability to Predict Skin Cancer 
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-02-02
2021-06-11
2022-02-02
2022-02-09
e2022031
Dermatol Pract Concept
Introduction: Actinic keratosis (AK) is a known indicator for sun damage, and subsequent squamous cell cancer may develop. The actinic keratosis and severity index (AKASI) is a recently developed tool that can evaluate both field cancerization and AK severity.
Objectives: We sought to evaluate if AKASI was a good predictor of cancer in AK patients and to compare AKASI with both the Physician Global Assessment (PGA) and total lesion count (TLC).
Methods:  Ninety patients with AK were included in the study. Each patient was examined, and AKs were scored with AKASI, PGA and TLC by 2 dermatologists. The AKASI, PGA and TLC values were compared between patients with skin cancer and patients without skin cancer.
Results: Mean AKASI, PGA, and TLC scores were 4.9, 1.7 and 9 respectively. The patients with skin cancer had higher scores of AKASI, PGA and TLC compared to the patients without skin cancer (P = 0.022, P = 0.014, P = 0.005, respectively). AKASI, PGA and TLC were very strongly correlated with each other (P &lt; 0.001). The AKASI threshold value for NMSC was determined to be 5.1.
Conclusions: AKASI, PGA and TLC may be used in the assessment of the severity of AK in daily practice or studies and may be considered as valuable tools in determining high-risk patients and to choose treatment option. AKASI seems to have an advantage to give a numeric threshold value for skin cancer.
Isil Karaarslan
2022/02/02
10.5826/dpc.1201a31
e2022031
Ege University, Medical Faculty, Department of Dermatology and Venereology, Izmir, Turkey
2160-9381
total lesion count
en
e2022031
Dréno B, Cerio R, Dirschka T, et al. A novel actinic keratosis field assessment scale for grading actinic keratosis disease severity. Acta Derm Venereol. 2017;97(9):1108-1113. DOI: 10.2340/00015555-2710. PMID: 28536731.
Comparison of Actinic Keratosis and Severity Index with Physician Global Assessment and Total Lesion Count and the Ability to Predict Skin Cancer 
https://dpcj.org/index.php/dpc/article/download/1838/1463
                    Dermatology Practical & Conceptual


 Comparison of Actinic Keratosis and Severity Index
 with Physician Global Assessment and Total Lesion
    Count and the Ability to Predict Skin Cancer
                                                 Ayda Acar1, Isil Karaarslan1


1 Ege University, Medical Faculty, Department of Dermatology and Venereology, Izmir, Turkey



Key words: actinic keratosis, AKASI, physician global assessment, skin cancer, total lesion count
Citation: Acar A, Karaarslan I. Comparison of actinic keratosis and severity index with physician global assessment and total lesion count
and the ability to predict skin cancer. Dermatol Pract Concept. 2022;12(1):e2022031. DOI: https://doi.org/10.5826/dpc.1201a31
Accepted: August 14, 2021; Published: January 2022
Copyright: ©2022 Acar and Karaarslan. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Ayda Acar, MD, Department of Dermatology, Ege University Faculty of Medicine, University Street Bornova, Izmir,
Turkey. E-mail: aydaerbas@yahoo.com




  ABSTRACT             Introduction: Actinic keratosis (AK) is a known indicator for sun damage, and subsequent squamous
                       cell cancer may develop. The actinic keratosis and severity index (AKASI) is a recently developed tool
                       that can evaluate both field cancerization and AK severity.
                       Objectives: We sought to evaluate if AKASI was a good predictor of cancer in AK patients and to
                       compare AKASI with both the Physician Global Assessment (PGA) and total lesion count (TLC).
                       Methods: Ninety patients with AK were included in the study. Each patient was examined, and AKs
                       were scored with AKASI, PGA and TLC by 2 dermatologists. The AKASI, PGA and TLC values were
                       compared between patients with skin cancer and patients without skin cancer.
                       Results: Mean AKASI, PGA, and TLC scores were 4.9, 1.7 and 9 respectively. The patients with skin
                       ­cancer had higher scores of AKASI, PGA and TLC compared to the patients without skin cancer
                        (P = 0.022, P = 0.014, P = 0.005, respectively). AKASI, PGA and TLC were very strongly correlated
                        with each other (P < 0.001). The AKASI threshold value for non-melanoma skin cancer was d
                                                                                                                ­ etermined
                        to be 5.1.
                       Conclusions: AKASI, PGA and TLC may be used in the assessment of the severity of AK in daily prac-
                       tice or studies and may be considered as valuable tools in determining high-risk patients and to choose
                       treatment option. AKASI seems to have an advantage to give a numeric threshold value for skin cancer.




Original Article | Dermatol Pract Concept. 2022;12(1):e2022031                                                                           1
Introduction                                                        The scalp constitutes 40% of the head region, and each of
                                                                    the other areas constitutes 20%. For each of the 4 areas, the
Actinic keratoses (AK) are hyperkeratotic lesions on sun-dam-       percentage of actinic damage is scored 0 to 6. The most prom-
aged skin characterized by atypical epidermal proliferation of      inent AK distribution, erythema, and thickness are assessed
keratinocytes that have a potential for malignant transfor-         from 0-4. The maximum AKASI value is 18. The pivotal study
mation to squamous cell carcinoma (SCC). They are gener-            proposed an AKASI score of 2.9 as mild, 5.3 as moderate, 8.3
ally asymptomatic, erythematous, or pigmented papules or            as severe, 8.7 as very severe [12].
plaques with scales, located on sun-exposed areas like the
face, scalp, ear helices, and dorsum of the hand [1]. Excessive
exposure to ultraviolet (UV) radiation is the major cause           Objectives
of AK. Fairer skin types, older age, chronic use of systemic
                                                                    In the literature, the data on the association between
immunosuppressive drugs, and exposure to arsenic have also
                                                                    non-melanoma skin cancer and AKASI, PGA, and TLC is
been described as risk factors [2-4]. In addition to immuno-
                                                                    limited [14]. In this study, we sought to evaluate this asso-
suppressive drugs, other drugs, such as voriconazole, calcium
                                                                    ciation and discuss the ability of these methods to predict
channel blockers, BRAF inhibitors, hedgehog inhibitors,
                                                                    skin malignancy.
hydroxyurea, and psoralen plus UVA therapy have been
linked to a higher risk for AK and SCCs [5-8]. On the other
hand, oral retinoids and nicotinamide have been linked to a
                                                                    Methods
reduction in the risk of AK and SCC [9].
    The estimated risk for an individual AK to transform            The study was approved by the local ethics committee (no:
into SCC has been reported to be 0.075%-0.096% annually             70198063-050.06.04). Patients with AK, who were referred
[2]. Although most of AKs regress spontaneously or persist          to our dermato-oncology unit within a 6-month period and
without a malignant transformation, the major concern is            who signed the informed consent form, were involved in
the difficulty in estimating which lesion might have a higher       the study. Patients with a history of photosensitivity, non-
potential for malignancy. The thickness or hyperkeratosis of        melanoma skin cancer (NMSC)-prone genodermatoses, and
an individual AK lesion does not have equal SCC progres-            melanoma were excluded.
sion risk [10]; thus, treatment is highly recommended for              A detailed anamnesis on accompanying diseases, drug
each AK lesion. In recent years, the term field cancerization       usage, previous history of NMSC, duration of the present
(FC), which describes an area of severe sun damage with             lesions, and the Fitzpatrick skin type were recorded. A
multiple AKs, telangiectasia, wrinkles, dyschromia and elas-        total-body skin and dermoscopic examination were per-
tosis, has been proposed [11] and FC treatment has been             formed for each patient. The patients were examined by
recommended for a better management of the patients [3].            2 dermatologists at the same time in order to avoid any
The identification of patients with a higher risk for malig-        interobserver variability. The AKASI, PGA and TLC values
nant transformation is another important issue to consider          were noted.
when deciding which patients should be included in a closer            Descriptive statistics of the data were given as mean,
follow-up program.                                                  standard deviation, median, minimum, maximum, frequency
    There have been some efforts to grade the risk of patients      and percentage values. Normality assumption of quantitative
with malignant potential. The Physician Global Assessment           data was checked by Shapiro-Wilk test. Independent sample
(PGA) scale is a subjective assessment tool that allows the         t-test was used for variables with normal distribution, while
physician to evaluate the overall situation of the patient [12].    Mann-Whitney U test and Kruskal-Wallis test (Dunn test
PGA grades AKs in five categories (0: clear, 1: almost clear,       for paired comparisons) were used for variables that did
2: mild, 3: moderate, 4: severe) [12]. The total lesion count       not provide the assumption of normality. The correlation
(TLC), in which physician counts the clinically evident AK          of quantitative data with each other was evaluated with
lesions, is another suggested way to evaluate a patient both        Spearman Rho correlation coefficient. Relationships between
before and after the therapy [13]. Recently, the actinic kera-      categorical variables were examined using the Pearson
tosis and severity index (AKASI) has been suggested [12]. The       Chi-square test. A receiver operating characteristic (ROC)
AKASI supplies a numerical score on an index and evaluates          analysis was used to determine a cutoff point for diagnostic
both the severity of AK and FC (Table 1) [12]. AKASI has also       methods. Statistical analysis was performed using IBM SPSS
been reported to be useful in monitoring treatment outcomes         Statistics 25.0 (IBM SPSS Statistics for Windows, Version
[10]. In AKASI score, the head is divided into 4 regions: scalp,    25.0, IBM) package program. The significance level was set
forehead, left face (cheek, ear, chin, and nose), and right face.   at 0.05 in all analyses.




2                                                                       Original Article | Dermatol Pract Concept. 2022;12(1):e2022031
Table 1. Definition of Components of Actinic Keratosis Area and Severity Index (AKASI) and How to
                                     Calculate AKASI Score*

                                                      Evaluation of AKASI [12]


     AKASI Components                                                         Definitions

 Solar damage (SD)                  Head is divided to 4 areas: scalp (S), forehead (F), right half of the face (R), left half of
                                    the face (L).
                                    Skin with solar damage for each of the 4 areas is estimated and scored 0-6.
                                    0 (0%), 1(1-9%), 2(10-29%), 3(30-49%), 4(50-69%), 5 (70-89%), 6 (90-100%).

 Distribution of AK (D)             0                   No AK


                                    1                   Isolated or scattered AK

                                    2                   Clustered (Small clusters up to 25 cm2)
                                    3                   Clustered and confluent (AKs are coalescing in a cluster of <25 cm2)
                                    4                   Confluent (AKs are coalescing and cannot be easily distinguish)

 Erythema of AK (E)                 0                   No erythema
                                    1                   Slight red
                                    2                   Moderate red
                                    3                   Intense red

                                    4                   Very intense red
 Thickness of AK (T)                0                   No palpable or visible AK
                                    1                   Just palpable AK
                                    2                   Clearly palpable
                                    3                   Thickened
                                    4                   Very thickened

 Total AKASI score                  0.4 x (D+E+T+SD of scalp) + 0.2 x (D+E+T+SD of forehead) + 0.2 x (D+E+T+SD of right
 (0-18)                             face) + 0.2 x (D+E+T+SD of left face)

*Adapted from the report of Dirschka et al [12].

AK = actinic keratosis; AKASI = actinic keratosis area and severity index.




Results                                                               suppressive drugs, and 1 patient was receiving hydroxyurea.
                                                                      The distribution of Fitzpatrick skin type was as follows: 73
A total of 90 patients were involved in the study. Fifty-four         patients (81%) had Fitzpatrick skin type II and 17 patients
patients (60%) were males. The age range was 48-87 years              (19%) had type III. The duration of the present AK lesions
(mean age was 69 years and median age was 71). The accom-             ranged from 2 months to 30 years. The mean duration was
panying diseases were hypertension (43%), diabetes mellitus           7 years. Mean AKASI was 4.9, mean PGA was 1.7 and mean
(27%), coronary arterial disease (CAD) (14%), solid organ             TLC was 9.3. Mean AKASI was 6 in male patients and 3
malignancy (13%), inflammatory or autoimmune skin dis-                in female patients. The difference between male and female
eases (13%), solid organ transplantation (6%) and others              patients was statistically significant (P < 0.001). Mean PGA
(asthma, vertigo, Parkinson disease, migraine, gut, essential         was 2 in male and 1 in female patients. Mean TLC was 11 in
thrombocytosis, familial Mediterranean fever, hepatitis B)            male and 7 in female patients. The difference between male
(10%). Fourteen patients (16%) were receiving calcium                 and female patients of PGA and TLC was statistically signif-
channel blockers, 9 patients (10%) were receiving immuno-             icant (P < 0.001, P = 0.002).




Original Article | Dermatol Pract Concept. 2022;12(1):e2022031                                                                      3
     Fifty-one patients (57%) did not have any current skin      P = 0.010, P = 0.016). Mean and median AKASI, PGA
cancer or skin cancer history. A total of 39 patients (43%)      score and TLC were higher in group A (mean 6, median
had a current skin cancer and/or past history of skin cancer.    6; mean 2, median 2; and mean 11, and median 11,
Among them, 28 patients (31.1%) had only previous skin           respectively) compared to group B (mean 4, median 4;
cancer history, 8 patients (8.8%) had only concurrent skin       mean 2, median 1 and mean: 8, and median 7, respec-
cancer, and 3 patients (3.3%) had both concurrent skin cancer    tively) (Table 2). The higher scores of AKASI, PGA and
and previous skin cancer history. Nineteen patients (21.1%)      TLC in group A were statistically significant (P = 0.022,
had only basal cell carcinoma (BCC) and BCC count was 26.        P = 0.014, P = 0.005).
Thirteen patients (14.4%) had only SCC and SCC count was            Nineteen patients with high risk drugs or diseases for
21. Seven patients (7.7%) had both SCC and BCC, tumor            skin cancer had higher AKASI scores and it was statistically
count was 29 (11 for SCC and 18 for BCC). One patient            significant (P = 0.033). These patients had also higher mean
who had both BCC and SCC also had 2 basosquamous cell            PGA and TLC values, which were not statistically significant
carcinomas. Total tumor count was 78 (44 for BCC, 32 for         (P = 0.077, P = 0.221).
SCC, and 2 for basosquamous cell carcinoma). In all but 7           Patients were also grouped as no skin cancer (group
patients all the tumors were located on the face or scalp. In    I, n = 51 patients), patients with only BCC (group II, n
7 patients, 14 tumors (8 BCCs and 6 SCCs) were located on        = 19 patients), patients with only SCC (group III, n = 13
an extremity or trunk. None of the patients had skin cancer      patients), and patients with both BCC and SCC (group IV,
metastasis.                                                      n = 7 patients). Mean AKASI score, PGA, and TLC were
     All items were compared between the group with              highest in group IV. The ranking of mean values of scores
previous or present skin cancer (Group A, n = 39) and            was: group III, II, and I respectively. The increase in the mean
the group with no history of skin cancer (Group B, n =           values of AKASI, PGA, and TLC from group I to group IV
51) (Table 2). The mean age in group A was 70 years              was statistically significant (P = 0.026, P = 0.026, P = 0.038).
(median 73 years), and the mean age in group B was 69            The total number of skin cancer counts (previous and present)
years (median 70 years). The mean age of the patients            were not related with AKASI, PGA, and TLC (P = 0.064, P =
was higher in the group with skin cancer, but it was not         0.075, P = 0,149).
statistically significant (P = 0.261). Mean and median              AKASI, PGA, and TLC were correlated with each
AK duration was longer in the group A (mean 9, median            other (P < 0.001). Correlation between AKASI and PGA,
9) compared to the group B (mean 6, median 5). Hav-              between AKASI and TLC, and between PGA and TLC were
ing longer AK duration in the group A was statistically          very strong (r = 0.881, r = 0.893, r = 0.849). As a result of
significant (P = 0.009). The distribution of demographic         ROC analysis, the AKASI threshold value for total NMSC
features and scores of AKASI, PGA and TLC in the two             was determined to be 5.1 (P = 0.022, area = 0.642). The
groups are shown in Table 2. There was no statistically          AKASI thresholds for SCC and BCC according to ROC
significant relationship between having skin cancer and          analysis were 5.5 (P = 0.056, area = 0.682) and 6.9 (P =
gender (P = 0.794), or accompanying diseases. However            0.926, area = 0.509), respectively. Total NMSC threshold
statistically significant relationship was found with not        value was statistically significant. However, threshold val-
having CAD (P = 0.028). AK duration was significantly            ues for only BCC or only SCC groups were not statistically
related with AKASI, PGA and TLC scores (P = 0.038,               significant.




    Table 2. Comparison Between the Group with Previous or Present Skin Cancer (Group A) and the
                         Group with No History of Skin Cancer (Group B).
                                                                Group A                                 Group B
 Male percent                                                    62%                                      59%
 Mean and median age                                             70, 73                                   69, 70
 Mean and median AK duration (years)                              9, 9                                     6, 5
 Mean and median AKASI                                            6, 6                                     4, 4
 Mean and median PGA                                              2, 2                                     2, 1
 Mean and median TLC                                             11, 11                                    8, 7

AK = actinic keratosis; AKASI = actinic keratosis area and severity index; PGA = Physician Global Assessment; TLC = total
lesion count.




4                                                                    Original Article | Dermatol Pract Concept. 2022;12(1):e2022031
Conclusions                                                               Our study employed AKASI, PGA and TLC to assess the
                                                                    severity of AK and to evaluate the relationship with malig-
In order to determine the malignant transformation risk in          nancy risk. We conclude that AKASI, PGA, and TLC may be
AK, there is a need for scoring the disease extent and overall      used in the assessment of the severity of AK in daily practice
severity rather than evaluating the individual lesion. PGA          or studies. Although a longer period is needed for calcula-
and TLC have been used for determining the severity of AK.          tion of AKASI, it seems advantageous to have a numerical
Recently, in 2017, AKASI was proposed by Dirschka et al             threshold value for skin cancer. This is the second study that
[12]. In 2018, Pellacani et al compared AKASI with TLC [13]         evaluates this threshold value in the literature. To establish a
and found AKASI a reproducible method that can be used in           common value, more studies are needed.
clinical trials as an alternative to TLC. Although no significant
difference was found between AKASI and TLC in the interob-
server variability, AKASI had a slightly higher intra-class cor-    References
relation coefficient compared to TLC. They stated that either
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6                                                                             Original Article | Dermatol Pract Concept. 2022;12(1):e2022031
