Clinical Patterns and Disease Related Morbidity Assessment of Chronic Urticaria

Research Article

Open Access

Malathi M¹, Devinder Mohan T^1*, Mariette D’Souza¹, Amiya KN¹, Rashmi K¹ and Mahalakshmy T²

¹Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

²Indira Gandhi Medical College and Research Institute, Puducherry, India

^*Corresponding authors:

Dr. Devinder Mohan Thappa
Professor and Head
Department of Dermatology and STD
Jawaharlal Institute of Postgraduate Medical Education and Research
Puducherry 605006, India
Tel: 914132272380, 919443958975
Fax : 91413 2272735
Email: dmthappa@gmail.com

Received April 24, 2012; Published August 29, 2012

Citation: Malathi M, Devinder Mohan T, Mariette D’Souza, Amiya KN, Rashmi K (2012) Clinical Patterns and Disease Related Morbidity Assessment of Chronic Urticaria. 1:282. doi:10.4172/scientificreports.282

Copyright: © 2012 Malathi M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Chronic urticaria is a debilitating disease causing significant psychological, social and occupational distress to the patients thereby adversely affecting their quality of life. This study was done to clinically characterize the pattern of chronic urticaria and to assess the disease-related morbidity in these patients in our institution using a newly devised 6-point functional impairment rating scale and a modified urticaria severity score.

Methods: This descriptive study was conducted in 204 consecutive patients with chronic urticaria attending the Dermatology out-patient department of a tertiary care referral centre over a period of two years. The severity of pruritus was assessed using visual analogue score (VAS) and a newly devised 6-point functional impairment rating scale. The severity of urticaria was assessed using an enhanced urticaria severity score which was modified by adding a new disease duration score.

Results: The distribution of chronic urticaria was as follows: chronic autoimmune urticaria (CAU) and chronic idiopathic urticaria (CIU) in 48 (23.5%) patients each; physical urticaria (PU) in 27 (13.2%) patients; urticarial vasculitis (UV) in 2 (1%) patients; PU in combination with CIU in 62 (30.4%) patients and PU in combination with CAU in 17 (8.3%) patients. Angioedema coexisted in 54.4% of patients. Female gender and PU overlapping with other types of urticaria were associated with a higher severity. There was a good correlation between VAS and our newly devised functional impairment rating scale. The enhanced urticaria severity score with added disease duration appears to be a better assessment scale for few specific types of chronic urticaria.

Conclusions: A large proportion of PU can overlap with the other types resulting in an increased severity which is better assessed by adding a new disease duration score. The 6-point functional impairment rating score would be a better indicator of the severity of pruritus than VAS.

Keywords

Chronic urticaria, angioedema, urticaria severity score, visual analogue score, functional impairment rating scale

Abbreviations

PU: Physical Urticaria; CIU: Chronic Idiopathic Urticaria; CAU: Chronic Autoimmune Urticaria; UV: Urticarial Vasculitis; DERM: Symptomatic Dermographism; DPU: Delayed Pressure Urticaria; CHOL: Cholinergic Urticaria; ADR: Adrenergic Urticaria; COLD: Cold Urticaria; VAS: Visual analog scale; ASST: Autologous Serum Skin Test; QoL: Quality of Life; CU-Q₂oL: Chronic Urticaria: Quality of Life Questionnaire; USS: Urticaria Severity Score

Introduction

Urticaria is a common problem, with a point prevalence of 0.1% affecting at least 15-20% of the population at some point in their lives [1]. Chronic urticaria affects approximately 1% of the population [2,3] and encompasses physical urticaria, contact urticaria, urticarial vasculitis, chronic autoimmune urticaria, chronic urticaria due to known provoking factors and chronic idiopathic Urticaria [1,4]. Despite improvements in our understanding of its pathogenesis, the condition still remains a vexing problem for many patients with varying degree of morbidity. The psychological, social and occupational distress, caused by chronic urticaria is comparable to that of patients awaiting coronary artery bypass surgery [5,6].

The etiologic and treatment aspects of chronic urticaria has always been the focus of many previous studies [7,8], but there are only a few studies that give importance to the impact of chronic urticaria on the quality of life (QoL) [8]. Hence this study was undertaken to assess the disease related morbidity of chronic urticaria using a newly devised 6-point functional impairment rating scale in addition to the routine visual analogue score (VAS) used for assessment of pruritus. Though VAS is adequate in assessing the severity of the symptom, it does not take into account the other aspects of pruritus, such as the relative impact of pruritus on the QoL and the functional disability caused by this symptom. 9 VAS may fail to detect changes in pruritus severity in some patients owing to their difficulty in translating a subjective symptom into a point on a line [9]. Moreover, chronic urticaria quality of life questionnaire (CU-Q₂oL), which is hitherto the only disease specific questionnaire for chronic urticaria [10] requires cross-cultural adaptations as patient perception of disease and QoL can vary in different cultural contexts. Till date CU-Q₂oL has been validated for use only in some countries [7,11-15]. Since there was no validated Indian version of the questionnaire during the period when the study was undertaken and the generic health-related QoL measures are tedious and time consuming, we devised this simple, practical, convenient tool - the 6 point functional impairment rating scale to assess the disease related morbidity of chronic urticaria. We also analyzed the clinical patterns of the different types of chronic urticaria and their combinations, as there is a dearth of data in this regard.

Methods

This descriptive study was performed in all patients with chronic urticaria (urticaria with or without angioedema lasting for more than 6 weeks) attending the Dermatology Outpatient Department (OPD) of a tertiary care referral centre, from November 2007 to August 2009, after obtaining their written informed consent. Approval from the Institute Research Council and Institute Ethics Committee was obtained.

The study subjects were interviewed by the first author using a predesigned, pre-tested semi-structured interview schedule in the native language (Tamil). During the interview a detailed history regarding the characteristics of urticaria and angioedema, associated symptoms and severity was obtained.

The severity of pruritus was assessed using a pre-tested ten point VAS and a newly devised 6 point functional impairment rating scale. The items for functional impairment rating scale were derived from review of the pruritus literature [9,16-18] and clinical experience of the authors. The rating scale as adapted by us for the assessment of pruritus is as follows: 0 - No pruritus; 1 - Tolerable and does not prevent any activities; 2 - Tolerable but prevents some activities; 3 - Intolerable but does not prevent basic activities; 4 - Intolerable and prevents basic activities; 5 - Intolerable and prevents verbal communication; 6 - Intolerable to the extent of suicidal thoughts.

We used the scoring system of Irinyi et al [19] (modified from Breneman et al) [20] instead of the standard urticaria severity score (USS) [21] to assess the urticaria severity. This was done because, the Iryni et al [19] score was an enhanced score, including all factors indicating severity like frequency of episodes, duration of weal, size of weals, extent of involvement, and pruritus intensity. The standard USS comprises only of pruritus intensity and number of weals [21]. Moreover during the preliminary study we observed that our patients had difficulty in stating the number of weals but localizing the extent of involvement and the size of weals was not difficult. A recent study has also proved that enhanced USS including weal size has adequate measurement properties to support its use in clinical research [22]. In our study, we further modified the Iryni et al [19] scoring system by including an additional disease duration score because the overall duration of chronic urticaria is likely to be longer in patients with higher disease severity [23]. Thus, we had two total severity scores - with and without disease duration (Table 1).

Table 1: Urticaria severity score.

In patients with history suggestive of physical urticarias (PU) and contact urticaria, relevant clinical tests were done to confirm the diagnosis. Chronic autoimmune urticaria (CAU) was diagnosed based on positive autologous serum skin test (ASST) and the remaining patients were diagnosed to have chronic idiopathic urticaria (CIU). A skin biopsy was performed to confirm the diagnosis in suspected urticarial vasculitis (UV). Patients who had both spontaneous as well as inducible urticarias were classified as separate groups based on positive or negative ASST into PU coexisting with CAU or CIU respectively.

The data was analyzed using the SPSS^® 13.0 for Windows^® (SPSS, Chicago, Illinois, USA). The data was summarized as percentages, mean, standard deviation and median. For comparison of means, oneway ANOVA or unpaired t test was used. If ANOVA was significant a post hoc test was done. A p-value of < 0.05 was considered statistically significant. The degree of correlation between VAS and the new 6-point functional impairment rating score was assessed using Pearson’s correlation coefficient. The distribution pattern of chronic urticaria in our study is represented as a Venn diagram (Figure 1).

Figure 1: Distribution of the types of chronic urticaria and combinations of the subtypes.

Results

Two hundred and four patients with chronic urticaria including 75 men and 129 women participated in the study. The mean (± SD) age of the study population was 34.94 (± 13.55) years (ranging from 5-72 years with a median of 35 years). The mean (± SD) age at onset of urticaria was 32.13 (± 13.66) years (ranging from 2-72 years with a median of 32.50 years). Ten (4.9%) patients were children less than fifteen years of age.

Clinical patterns of chronic urticaria

The distribution of the various types of chronic urticaria along with its various combinations is depicted in Figure 1 and their characteristics are summarized in Table 2.

Table 2: Demographic and clinical characteristics of the different types of chronic urticaria.

Angioedema co-existed with urticaria in 111 (54.4%) patients (Table 2). Angioedema was associated with pruritus in 65 (65/111, 58.6%) patients, pain in 36 (36/111, 32.4%) patients and breathlessness in 26 (26/111, 23.4%) patients. The most common sites involved were the lips in 89 (89/111, 77.4%) patients, followed by the periorbital region in 58 (58/111, 45.9%) patients.

Morbidity assessment of chronic urticaria

The mean (± SD) duration of the disease was 34.76 (± 57.63) months ranging from 2 months to 49 years with a median of 12 months. Majority of patients (123, 60.3%) had the disease for more than one year duration.

Pruritus scoring could be done only in 200/204 patients as four children (age < 5 years) unable to understand VAS were excluded. The mean (± SD) VAS was 6.96 (± 2.31). Higher intensity VAS (6-10) was noted in 141 (70.5%) patients. The most commonly reported VAS was 10/10 as reported by 49 (24.5%) patients. The mean VAS (± SD) was higher in women [7.54 (± 2.26)] than that in men [5.96 (± 2.08)] and this difference was statistically significant (p < 0.001 by t test). The mean (± SD) 6-point rating score of functional impairment was 3.69 (± 1.60). A higher intensity of functional impairment rating score (4-6) was noted in 104 (52%) patients. The most commonly reported functional impairment rating scores were 2 and 3 in 39 (39/200, 19.5%) patients each. The mean (± SD) functional impairment rating score was higher in women [4.03(±1.59)] when compared to men [3.08(±1.45)] and the difference was statistically significant (p < 0.001 by t test). The genderwise distribution of VAS and 6-point functional impairment rating scores is provided in Figure 2a and Figure 2b respectively. The 6-point functional impairment rating scores correlated with VAS score with a Spearman correlation co-efficient of r = 0.86 (95% CI =0.82 - 0.89, p< 0.0001).

Figure 2: Distribution of (a) VAS scores and (b) 6-point functional impairment rating scores.

Majority (157/204, 77%) of the patients had a daily occurrence of weals. The individual weals lasted for a mean (± SD) duration of 2.14 (± 2.65) hours, ranging from 5 minutes to 12 hours with a median of one hour. The duration of weals in urticarial vasculitis was excluded from the analysis as they were outliers. One hundred and forty nine (149/204, 73%) patients had weals distributed all over the body and the distribution of occurrence of weals is shown in Figure 3. The mean size of the individual weal was 3.34 cm ranging from 2 mm to 10 cm excluding symptomatic dermographism where in the size of the lesions could not be assessed. Occurrence of weals at night was the commonest (113 patients, 55.9%) and 68 (33.3%) patients had no diurnal variation. Pruritus was reported in all patients and a sensation of warmth was the next major symptom noted in 128 (128/204, 62.7%) patients followed by the other symptoms as shown in Figure 4.

Figure 3: Site of occurrence of weals in chronic urticaria.

Figure 4: Symptoms associated with weals apart from pruritus.

Urticaria severity score

Total urticaria severity score was analyzed in185 patients only, as those who had dermographism alone, cold urticaria alone, adrenergic urticaria alone and four children in whom VAS could not be assessed were excluded.

The mean urticaria severity score in men and women is displayed in Table 3. Women had a statistically significant higher pruritus intensity and total urticaria severity scores (with and without disease duration score) when compared to men. Table 4 represents urticaria severity score in the different types of chronic urticaria. Table 5 represents the components of the urticaria severity score in the different age groups. Table 6 provides the statistically significant comparisons of the urticaria severity scores among the various combinations of chronic urticaria. In patients with a functional impairment rating score of 6/6 (suicidal ideations), the USS was higher when compared to the other patients [mean (± SD) total urticaria severity score without duration - 12.68 (±1.51) versus 11.0 (± 2.24); and, mean (± SD) total urticaria severity score with duration - 14.31 (± 1.73) versus 12.48 (± 2.46)] and this difference was statistically significant.

Table 3: Urticaria Severity Score in the study group and comparison of the score between males and females (N=185)*.

Table 4: Comparison of urticaria severity score (N=185*) among the different types of chronic urticaria.

Table 5: Comparison of urticaria severity score (N=185*) among the different age groups.

Table 6: Comparison of urticaria severity score between different combinations of chronic urticaria.

Discussion

Chronic urticaria a major health problem causing patients’ distress predominantly affects the middle-aged population and more commonly women. This female preponderance noted in our study as well as in several other previous studies [19,24-29] might reflect the autoimmune pathogenesis of chronic urticaria which correlates with the higher frequency of autoimmune diseases in women. Conforming to the above statement, we had observed chronic autoimmune urticaria to have the highest female to male ratio (3:1) compared to other types of chronic urticaria.

The long duration, high intensity of pruritus and predominantly daily episodes with occurrence of weals all over the body, as evident from our study as well as earlier studies [25,30] makes chronic urticaria a debilitating disease with significant negative impact on the QoL. Chronic urticaria can be associated with psychiatric symptoms like irritability, depression, and anxiety and stress, which may play a role in the genesis of the disease as well as in its evolution [31,32]. In our study, five women had attempted suicide due to their inability to cope up with the severity of the disease. Moreover, it was observed that none of the patients with suicidal ideations had any documented psychiatric disturbance. This indicates the extent of debilitation caused by chronic urticaria, thus impairing the quality of life significantly.

We found our new 6-point functional impairment rating score to greatly correlate with VAS with a Spearman correlation co-efficient of r = 0.86. To compute the total USS, only VAS was used. Despite the 6-point functional impairment rating score not being included in the total USS, the latter was truly higher in patients with suicidal ideations. The advantages of our new 6 point functional impairment rating scale are: it is easier to use and comprehend, coding as well as interpretation is much easier when compared to VAS. It also takes lesser time to explain patients and was also found to be easier for young children or their parents to comprehend and answer precisely when compared to VAS. Hence, it can serve as a better tool for the quick assessment of morbidity in routine evaluation of patients in outpatient settings in India, and can also be used to evaluate the impact of treatment response during follow up.

We found that adding disease duration to the USS improved the detection of statistically significant severity of a few types of chronic urticaria. The longer duration of urticaria is associated with four factors namely disease severity, angioedema, combination of chronic spontaneous urticaria with physical urticaria and autoreactivity (ASST positivity) [23]. Similarly, the duration of chronic urticaria was more prolonged when CAU and DPU co-existed. While assessing USS without disease duration, we noted no statistically significant difference between CAU coexisting with DPU and CAU occurring alone, or between CAU coexisting with DPU and CIU coexisting with DPU i.e., CAU+DPU vs. CAU and CAU+DPU vs. CIU+DPU. But with the inclusion of disease duration, patients with CAU coexisting with DPU had a statistically significant higher severity score compared to CAU occurring alone and CIU coexisting with DPU. Thus, USS with added disease duration appears to be a better assessment scale for few specific types of chronic urticaria. We also observed patients with CAU to have larger weal size and higher total USS without disease duration when compared to those with CIU. The co-existence of dermographism with CIU also worsened the urticaria severity.

PU constitutes 20-30% of cases of chronic Urticaria [4] and it is quite common for multiple PUs to coexist 33-35 as well has for PU to coexist with CIU, [33,36-39] as observed from our study. DPU rarely exists alone and it usually presents with concomitant CIU 40, 41 as also observed from our study, wherein DPU did not occur alone and a large number of patients had DPU co-existent with CAU or CIU and symptomatic dermographism. Hence, it is essential to look for coexistent DPU in patients with CIU or CAU as it prolongs the duration and increases the severity of urticaria influencing the prognosis and management.

At least one episode of mild or severe angioedema occurs in upto 50% of cases of urticaria, [1,42] as observed in our study also. Champion et al [43] reported patients with angioedema to have a more severe disease with a more prolonged course and symptoms less responsive to therapy, as compared to patients having urticaria alone. Toubi et al [44] found no association between the presence of angioedema and the severity, but there was a significant association with the duration of urticaria. However, in our study, there was neither an increased severity nor an increase in the disease duration when angioedema coexisted with urticaria.

To conclude, chronic urticaria is predominantly a disease of middle-aged women. A large proportion of physical urticaria can overlap with the other types, resulting in an increase in the urticaria severity than when they exist alone. The addition of disease duration score to the existing total USS has led to the emergence of a new observation that the severity of urticaria is greater when CAU and DPU co-exist. Since VAS and 6-point functional impairment rating responses are highly correlated and the 6-point rating scores are easier to administer and interpret, this new functional assessment tool may be preferable to measure pruritus intensity in routine assessment of patients in outpatient settings, and may also provide a basis for future cross cultural studies on pruritus . However, these observations need to be confirmed with larger studies before standard use.

Acknowledgement

The authors wish to acknowledge the work of Dr. Karthikeyan V S and Dr. Hemachandren M for their assistance in the drafting and proof-reading of the manuscript.

References