Intestinal parasitic infestations in adult chronic spontaneous urticaria patients and the relation between them: A case–control study

INTRODUCTION

Urticaria is an allergic reaction characterized by smooth, edematous, erythematous, and itchy wheals. Usually, it lasts <24 h without post-inflammatory hyperpigmentation. Urticaria is classified as acute or chronic, depending on its duration. This condition is thought to affect at least 0.5–5% of the population. The possible causes of chronic urticaria (CU) are infections, dental caries, parasitic infestations, some types of food, thyroid diseases, and drugs.^[1,2] CU is a debilitating disorder that severely reduces the quality of life and has a considerable impact on the healthcare systems.^[3]

Chronic spontaneous urticaria’s (CSU) etiology is not yet fully understood. Mast cells and basophils, whose activation and degranulation cause histamine release, have been implicated. Mast cells also release cytokines and chemokines that are responsible for attracting the perivascular infiltration seen around tiny venules in the skin of CSU patients. CSU is hypothesized to be driven by autoimmunity, involving immunoglobulin (Ig)G and IgE autoantibodies as well as high-affinity IgE receptors. However, only a small proportion of patients satisfy all the criteria for autoimmunity.^[4] Parasitic infestations were first hypothesized as an underlying cause in a pediatric CSU patient with Giardia lamblia, but the role of parasites in the etiology of CSU and the pathogenic mechanisms were unclear.^[5,6] The objectives of this study were to detect the prevalence of intestinal parasitic infestations in patients suffering from CSU and evaluate the correlation between them.

MATERIAL AND METHODS

This was a case-control study with 100 consecutive patients suffering from CSU who sought treatment at our urticaria and immunity unit and 100 healthy individuals as group control who sought treatment at outpatient cosmetic and laser clinics of Cairo Hospital of Dermatology and Venereology. All patients were examined for stool analysis to detect intestinal parasitic infestations. The study received approval from the Training and Research Sector in the Ministry of Health and Population (Ethical Committee No: 20-2023/12) and was conducted from May 2023 to March 2024. The included cases were told about the goal of the investigation and informed written consent was obtained from the patients before enrollment in this study. Inclusion criteria were adults aged 20–60 years, of both sexes, diagnosed with CSU whereas, exclusion criteria were pregnant or lactating women and individuals with a history of malignancies. The sample size was calculated using the formula, n = Z1-a² P(1-P)/d², where n is the sample size, Z is 1.96 (with a 95% confidence level), and P is the predicted prevalence of intestinal parasite infestations in patients with urticaria = 0.145 (14.5%) according to the results of a systematic review study done by Kolkhir et al., 2016;^[7] and d = precision (margin of error) = 7% (0.07). Patients were asked about their age, gender, onset, course, and duration of CU, as well as any concomitant conditions and drug history. A general examination for signs of systemic disease and local examination for assessing the severity of urticaria by calculation of urticaria total severity score was carried out. The total severity score for urticaria was computed by adding six parameters: the number of wheals, the size of the wheals by measuring with a ruler, the intensity of the pruritus, the duration of the persistence of symptoms, the frequency of appearance, and the frequency of antihistamine usage (all patients were treated according to the European Academy of Allergy and Clinical Immunology [EAACI] guidelines). Each parameter’s score ranged from zero to three. Urticarial disease severity was graded as clear (0), mild (1–6), moderate (7–12), or severe (13–18) [Table 1].

RESULTS

This was a case-control study that included 100 healthy individuals as group control and 100 patients suffering from CSU. The mean age in the case group was 36.91 ± 10.47 years and the mean age in the control group was 35.94 ± 10.54 years, with no statistically significant difference between the two groups (P = 0.515). There were 39% males and 61% females in the case group, while there were 45% males and 55% females in the case group, with no statistically significant difference between the two groups (P = 0.390) [Table 2]. In the case group, the mean urticaria duration was 15.1 ± 11.7 months with a range between 3 and 48 months. The urticarial severity was classified as mild, moderate, and severe in 26%, 49%, and 25%, respectively.

DISCUSSION

CU is a multifaceted inflammatory skin illness caused by the activation and degranulation of cutaneous mast cells, followed by the release of histamine and other mediators that cause sensory nerve stimulation, vasodilation, plasma extravasation, and cellular recruitment. This mechanism induces the development of the disease-defining signs and symptoms, itchy hives, and angioedema (or both).^[7,8] Although urticaria is a widespread condition, its pathophysiology is poorly known. It is also unclear how intestinal parasite infections affect CU and whether they might cause clinical signs of allergic reactions. Clinical observations may assist in discovering probable correlations between intestinal parasite infections and hypersensitivities.^[9] Our goal, based on this evidence, was to determine the prevalence of intestinal parasitic infestations in adult patients suffering from CU. This was a case-control study with 100 healthy individuals as the group control and 100 patients suffering from CU as the case group. In the current study, the age of the studied population ranged from 20 to 57 years, the mean age in the case group was 36.91 ± 10.47 years, and the mean age in the control group was 35.94 ± 10.54 years. Most research indicates that the peak age of CU occurrence is between 20 and 40 years. Therefore, patients are primarily affected during their working years and are more prone to absence and lower productivity due to the sickness and its treatment.^[10] A Spanish study found that the average age of patients was 35.75 ± 18.9 years, which is nearly similar to ours.^[11]

Urticaria can affect both sexes, but females are roughly twice as likely as males to develop it.^[12] This was in accordance with our results where we found the predominance of the female gender to be nearly twice the male gender (female [61%], and male [39%]), concurrent with what has been reported in previous studies.^[13-15] In contrast, Ban et al., discovered a lack of female predominance in the elderly CU group, despite a 57.9% prevalence of females in the overall study population.^[16] This finding is in concordance with a previous report of an almost equal sex distribution in an elderly CSU group.^[17]

The present study showed that in the case group, the mean urticaria duration was 15.1 ± 11.7 months with a range between 3 and 48 months. Dias et al. discovered that the mean time for illness progression was 10.6 years (3 months–60 years).^[18] In the study by Baiardini et al. the duration was shorter, approximately 1 year and 9 months.^[19] Gaig et al. discovered that 50% of CU patients were asymptomatic after 3 months and 80% after 12 months. However, 11% had affliction for over 5 years.^[20]

In the current research, the severity of urticaria was classified as mild, moderate, and severe in 26%, 49%, and 25%, respectively. This was consistent with the ASSURE trial, which revealed that almost 70% of patients had moderate-to-severe CSU, with an average urticaria duration of 5 years.^[21] Further, Ye et al., showed that the overall disease duration of CSU was roughly 4 years, with nearly half of patients classified as having moderate-to-severe CSU.^[22]

In this study, all patients were treated according to the EAACI guidelines.^[23] This guideline suggests the use of second-generation H1 antihistamines as the first line of treatment. Antihistamine use resulted in 72% of the cases responding, while 28% of them did not respond to antihistamines and needed a second line of treatment.

The present study showed that the prevalence of intestinal parasitic infestations in the stool was 66% in the case group which was statistically significantly higher as compared to the control group (16%) (P < 0.001). In line with our findings, Dhanabal et al. reported that the prevalence of intestinal parasitic infestations was 75.8% (194 of 256 stool samples were positive); and Entamoeba coli (23%), Cyclospora spp. (22.2%), E. histolytica (21.8%), G. intestinalis (14.4%), and Ascaris lumbricoides (6.2%) were the most prevalent parasites.^[24] However, in our research, E. histolytica was the most common parasitic infestation in CSU patients.

The prevalence of intestinal parasitic infestations in the present study was comparable to a previous study that was conducted in India and reported the prevalence of intestinal parasitic infestations ranged from 33% in urban patients as compared to 91% in rural patients.^[25] In a Turkish study, parasitic infestations were discovered in 38.8% of the CSU patients and 11.1% of the control group, with a statistically significant difference between the groups.^[4] In another study with 55 CSU patients, Blastocystis spp. was isolated in 20% of the patients and 11.6% of the controls, and the difference between the groups was found to be statistically significant.^[6] Vezir et al. determined that the prevalence of intestinal parasitic infestations was 18.4% and 22.3% of adult and pediatric CSU patients, respectively, with Blastocystis spp. being the most prevalent parasite, consistent with previous observations.^[26]

The current study revealed that there was no statistically significant difference in age, sex, and disease duration between the cases with different urticarial severity. Contrary to our result, Metin et al., observed that longer urticarial disease duration and positive autologous serum skin test were present in patients with more severe CSU.^[27]

This study showed a statistically significant higher rate of positive parasitic infestations in the cases that did not respond to a full dose of antihistamine and needed a second line of treatment (92.9%) as compared to the cases that responded to antihistamine only (55.6%) (P < 0.001). In a double-blind crossover study, Kosnik and Subic reported that the subgroup with severe urticarial disease antihistamine resistance was more likely to benefit from the addition of montelukast.^[28] Alkeraye and AlRuhaimi further demonstrated that montelukast is a viable therapy choice for people with CU who are not properly controlled with antihistamines.^[29]

CONCLUSION

In light of our findings, we believe that stool parasite screening would be advisable for patients who have urticaria with undetectable etiology. Therefore, patients of CSU should have stool analysis as a routine investigation, especially in severe cases or with poor response to antihistamine treatment.