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The clinical scoring systems of atopic dermatitis were analysed and compared. Some biological parameters that can correlate with the clinical score were also reviewed. After the definition of the disease based on validated clinical criteria, the second necessity was the availability of reliable severity scores to allow clinicians to verify the course of the disease and the efficacy of treatments. After many proposals, the SCORAD (SCORing Atopic Dermatitis), that required more than three years of work, was the first one that was validated. SCORAD is freely available from an internet site and can be easily calculated using dedicated software. EASI (Eczema Area and Severity Index) score has also been validated but it has been modified twice. Simpler systems include SASSAD (Six Area, Six Sign Atopic Dermatitis) and TIS score (Three-Item Severity score). In parallel, biological parameters were investigated. Eosinophil cationic protein, circulating basophils, major basic protein, soluble E-selectin, antistaphylococcal enterotoxin B, immunoglobulin E titres and macrophage-derived chemokine, can correlate significantly with the clinical score. The clinicians will not benefit directly from laboratory techniques and will employ clinical scores.
To study a disease with the criteria of quality that modern evidence-based medicine requires, a clear definition of the disease itself is naturally the first element to consider. Since a single, undisputed biological criterion is lacking, the definition of atopic dermatitis (AD) relies on clinical criteria that have passed the test of time (e.g. those established by Hanifin and Rajka) (1) or that have been validated (i.e. UK Working Party) (2). The second item deals with the necessity of having reliable severity scores to allow clinicians to verify the course of the disease depending on various factors, treatments included. The current scoring systems of AD permit the definition, in numerical terms, of the severity of the disease in a single patient in a more scientific way, and better calculation of the impact of one treatment on the disease. The importance of those scoring systems is emphasized by the increasing necessity for multicentric studies that are often carried out in different countries. The ultimate goal is to evaluate the same parameters as well as to minimize the interindividual differences of evaluation that could invalidate the value of the data of the study.
The same George Rajka who edited the famous diagnostic criteria of AD, proposed in 1989 (3) a very concise scheme that takes into account the simple sum of three parameters (extension, course and intensity) each with a value between 0 and 3. The maximum possible score is thus 9. Based on this system, AD can be classified as mild (total score 3–4), moderate (from >4 to <8) and severe (from >8–9).
Costa and co-workers (4), in the same year, evaluated two different systems and concluded that the simpler one was not only easier and more rapid to complete but was also more reliable, having less interindividual variability. Costa's score (Fig. 1) calculates the intensity of 10 signs and symptoms (from 0 to 7; 0 = absence, 7 = maximum) along with the involvement of 10 different symmetrical skin regions (from 0 to 3; 0 = absence of involvement, 3 = complete involvement). The total score (up to a maximum of 100: 70 from signs and symptoms and 30 from extension) is obtained by simple addition of the partial scores. The same authors admit that the choice of severity criteria was not made according to strict evidence and they also state that five criteria instead of 10 would yield similar results, given the fact that many clinical signs are never pure but are mixed with others.
Figure 1. Costa's score. The 10 signs and symptoms are listed on the left, while the of the 10 different skin areas can be calculated from the outline on the right.
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In 1991 Bahner et al. (5, 6) proposed a new score named ADASI (Atopic Dermatitis Area and Severity Index). This scoring system was based on the determination of the involved body areas by point counting. On body diagrams, involved areas are color-coded according to the severity of the skin changes (green for mild dermatitis, blue for moderate and red for severe eczema) and evaluated by applying a transparent grid. To obtain the ADASI score, the fractions of the areas are weighted and multiplied by the intensity of the itching. The resulting scoring values are analysed by trend-and-time series analyses. These methods allow a clear statistical evaluation in each individual case. However, complications in the application of the mathematical formulae did not favour the use of this scoring system.
In 1993 a task force of almost 30 European experts published a scoring system that required more than three years of work: the SCORAD (SCORing Atopic Dermatitis) (7) (Fig. 2). This system considers both objective signs (severity and extension) and subjective ones (pruritus and loss of sleep). This score has also been validated (8) in the following years and is freely available from an internet site (http://scorad.sante.univ-nantes.fr). In addition, a dedicated software (scoradcard®, Technology Project & Software Production; Web site: http://www.tpsproduction.com) authored by Pelosi and Tripodi has already been implemented to make the calculation of the score more rapid.
Figure 2. SCORAD. In addition to analogue parameters of Costa's score (A and B), subjective symptoms (c) are also considered and calculated in the final score.
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Despite the fact that SCORAD is one of the best validated systems and is suited for clinical trials, for some authors it is too complicated and time consuming for routine clinical use. A simplified SCORAD, the so-called TIS score (Three-Item Severity score) is based on the evaluation of erythema, oedema/papulation and excoriation on a scale of 0–3 (9). This score appears particularly suitable in general practice, for routine clinical use and for screening purposes in clinical trials while the original SCORAD offers a more detailed and comprehensive assessment and is indicated for research purposes.
In 1996 Berth-Jones elaborated (10) a less sophisticated system named SASSAD (Six Area, Six Sign Atopic Dermatitis). This score encompasses the evaluation of six signs in six body areas, each with a scale from 0 (absent) to 3 (severe). This score has proved to be a simple and effective tool for recording and monitoring disease activity. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of 0 (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, and trunk. The maximum score is 108. This system has the advantage of being very rapid to use (2 min for an expert; 10 min for a novice); its limits are represented by the fact that it does not include important parameters such as pruritus or loss of sleep. In addition, as with many other tested AD scoring indices, the SASSAD index is subject to significant interobserver variation, reflecting the difficulties of assessing the severity of eczema reliably and objectively (11).
The last score described in order of time is EASI (Eczema Area and Severity Index) (12). This is a rather complex scale. First it multiplies the percentage of the affected area of four cutaneous regions by a coefficient and then adds this number to the severity scores of four signs (Table 1). In our opinion EASI has two non-negligible limits:
Table 1. EASI (Eczema Area and Severity Index): calculation for patients 8 years of age and older*
|Body region||EASI Score †‡|
|Head/Neck (H)|| (E + I + Ex + l) × Area × 0.1|
|Upper limbs (UL)|| (E + I + Ex + l) × Area × 0.2|
|Trunk (T)|| (E + I + Ex + l) × Area × 0.3|
|Lower limbs (LL)|| (E + I + Ex + l) × Area × 0.4|
It has been conceived with parameters that are not applicable to children less than 2 years of age, which are often those more severely affected.
In contrast to SCORAD, it ignores the symptoms, namely it does not consider the pruritus that is the cardinal symptom of AD.
Therefore it was proposed to introduce those items. At present, the modified EASI (mEASI) includes a visual analogue scale for the pruritus (but not a second one for the loss of sleep) similar to that in the SCORAD in which the values in centimetres are transformed into a coefficient that is added to the standard EASI score. In addition, EASI measurements are time-consuming and require trained personnel, thereby limiting its application to large-scale epidemiological studies. Therefore a new variant of EASI, the Self-Administered EASI (SA-EASI) has been developed to allow a caregiver's self-administered assessment of the severity of his/her child's AD (13).
In conclusion, the absence of a common universally accepted standard can be seen, at least in part, as a sign of an old nationalism. The mEASI is surely better than the standard EASI and is almost as good in our opinion, as SCORAD. In favour of the SCORAD remains the fact that this system is less complex and is validated. We advise the use of the SCORAD in personal and particularly in interpersonal studies. Nevertheless it should always be kept in mind that this system, as every other, is not perfect (14) and requires a preliminary study and a certain training prior to becoming fruitful. Control studies have found poor agreement between different scoring systems in assessing the overall severity of AD, indicating that they cannot be used interchangeably (15). SCORAD, however, seems to be more reliable because one study demonstrated that most evaluations by the 98 nonexpert investigators were within the range of those carried out by experts, indicating that SCORAD can be used by investigators from different disciplines (16).
In parallel with the studies aimed at finding standard clinical parameters of scoring AD, other authors tried to evaluate biological parameters. Some data indicate that serum eosinophil cationic protein may be a helpful tool for monitoring disease activity in AD (17). Other data indicate that ‘activated’ circulating basophils in vivo and increased basophil releasability, in particular in response to C5a, may serve as markers for more severe AD (18). In a different study, the serum levels of major basic protein correlated significantly with the clinical score (19). The same group of researchers studied the soluble E-selectin and found that levels were significantly higher in AD than in normal controls. In addition, there was a significant correlation between serum soluble E-selectin and the clinical score. Finally, clinical improvement was associated with a decrease in both the clinical score and in soluble E-selectin levels, indicating that this substance may play a role in AD (20).
A different approach derived from the study of superantigenic exotoxins produced by Staphylococcus aureus and their specific immunoglobulin E (IgE) antibodies; Nomura et al. were able to correlate antistaphylococcal enterotoxin B IgE titres with the severity of AD (21). A different hypothesis stimulated the research of Toyoda et al.; these authors investigated the possible pathogenetic activity of neurogenic components, such as neurotrophic factors and neuropeptides in AD. The background of their studies derived from numerous in vitro and in vivo studies that had shown that nerve growth factor (NGF) and substance P (SP) can be associated with the pathogenesis of human allergic diseases. They found that patients with AD had significant increases in plasma levels of NGF and SP compared to controls; they also observed a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems including the grading system of Rajka and Langeland and the EASI. These data suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune–inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD (22).
Finally, Leung and co-workers studied the chemokines, molecules responsible for the trafficking of leucocytes to sites of inflammation, whose levels were previously shown to be increased in patients with AD. Serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon-γ inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) have been tested to verify their potential as useful markers for AD severity. In their study (23), serum MDC levels correlated with SCORAD and its extent and intensity components. Serum TARC concentration showed a weaker correlation with the extent and intensity of skin involvement but not with SCORAD. The median serum levels of MDC and EOX were also higher in children with moderate as compared to mild AD. The other chemokines did not correlate with AD severity. In conclusion, their results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children (23).
As can be seen from this brief review, the investigations tending to find a reliable clinical or laboratory parameter for assessing and grading the AD have been numerous. The clinicians, either the office dermatologist, the paediatrician or the general practitioner, will not benefit directly from sophisticated laboratory techniques and should more realistically look at clinical scoring systems. The availability of these systems through the internet will facilitate their use by all professionals. The Investigator's Global Assessment (IGA), which can be defined as the overall physician's overall assessment for the whole body (Table 2), is widely used in many clinical trials (24) but the definition of clinical scores is very subjective. Moreover, this term is often applied in a different sense (25). Therefore it cannot be compared with SCORAD which stands as the most precise and specific scoring system for AD.
Table 2. Investigator's global assessment (IGA): this assessment is the overall investigator's overall global assessment for the whole body
|0 = Clear||No inflammatory signs of AD|
|1 = Almost clear||Just perceptible erythema, and just perceptible papulation/infiltration|
|2 = Mild disease||Mild erythema and mild papulation/infiltration|
|3 = Moderate disease||Moderate erythema and moderate papulation/ infiltration|
|4 = Severe disease||Severe erythema and severe papulation/infiltration|
|5 = Very severe disease||Severe erythema and severe papulation/ infiltration with oozing/crusting|