Primary Hyperhidrosis: Prevalence, Severity, and Impact on Quality of Life among Jordanian Patients.

BACKGROUND: Primary hyperhidrosis (PHH) is characterized by idiopathic, focal, bilateral, and symmetrical excessive and exaggerated sweating with a major impact on the quality of life (QoL). To date, there are no studies about the prevalence of PHH in Jordan and in the Arab region. AIM: To assess the prevalence, severity, and characteristics of PHH in the Jordanian population as well as its impact on QoL.
MATERIAL AND METHODS: This study was conducted in five hospitals in Jordan and included 4,500 attendants of outpatient clinics who were evaluated for the presence of PHH. To assess the severity of hyperhidrosis (HH), we used the Hyperhidrosis Disease Severity Scale (HDSS). To evaluate the impact of HH on QoL, the Dermatology Life Quality Index (DLQI) questionnaire was answered by our patients, either digitally or on paper.
RESULTS: The overall prevalence of PHH in the Jordanian population was 3.2% (n = 144). The most common site was the axillae (63%), either isolated or in association with other sites. Both sexes were affected equally. The overall mean age of onset was 14.7 years. Positive family history was found in 35% of the patients. Nearly two-thirds of the patients presented with HDSS of 3 or 4. The impact on QoL was substantial with a mean DLQI of 12.8.
CONCLUSION: PHH prevalence in the Jordanian population is 3.2%, which has a major impact on QoL. This raises the need for addressing this disease to reduce its burden on patient lives. Copyright:

Introduction

HH is a skin disorder characterized by excessive and exaggerated sweating that exceeds the required physiologic level for thermoregulation.[1234] It is classified into primary hyperhidrosis (PHH) or secondary types. Secondary HH, which occurs mostly in generalized distribution, is caused by or associated with underlying systemic disorders such as infections, tumors, endocrine disorders, neurologic disorders, vasomotor disorders, medications, and a variety of other causes.[5678910] In contrast, PHH is idiopathic, most often focal, bilateral, and relatively symmetric, occurring mostly in the axillae, palms, soles, or craniofacial regions.[51112] The severity of PHH can be assessed through the Hyperhidrosis Disease Severity Scale (HDSS), which is a disease-specific, quick, and easily understood tool that provides a qualitative measure of the severity of the patient's condition based on how it affects daily activities.[13] A score of 3 or 4 indicates severe HH while a score of 1 or 2 indicates mild or moderate HH. There is a wide variation in the prevalence of PHH worldwide from as low as 0. 93% to as high as 14.7%.[11141516171819] Histopathologically, there are no changes in the shape, size, number, or density of sweat glands. Genetic predisposition through autosomal dominant genes has been postulated.[20] The 14q11.2-q13 locus has been identified to be associated with palmar HH in the Japanese population.[21]

PHH has a major impact on the quality of life (QoL), interferes with daily activity, affects nearly all aspects of patient life, and leads to psychological impacts such as anxiety and depression.[22232425] These negative impacts are similar to or greater than the negative impacts caused by chronic diseases such as psoriasis.[26] To date, there are no studies about the prevalence of PHH in Jordan and the Arab region; therefore, the aim of this study is to assess the prevalence and characteristics of PHH and to increase physicians and public awareness of its negative impact on patients' life.

Materials and Methods

This is a multicenter, observational, cross-sectional study that was approved by the ethical committee. It was held in five tertiary hospitals in Jordan during the period between November 2019 and March 2020.

A total of 4,500 attendants of outpatient clinics from different departments in these five hospitals were evaluated for the presence of PHH. The patients were selected randomly and they were visitors of dermatology and other departments' clinics. The patients who met the inclusion criteria were subjected to further evaluation. For each patient to be included in the study, the patient must fulfill the following eligibility criteria.

Inclusion criteria:

Meeting the diagnostic criteria for PHH.

Age less than 45 years, since PHH tends to ameliorate after the age of 45, and to rule out the misdiagnosis of PHH that results from night sweats and hot flashes of menopause.

Willing to participate in the study.

Exclusion criteria:

Presence of associated comorbidities that might lead to secondary HH including, but not limited to, infections (e.g., tuberculosis), tumors (e.g., lymphomas and pheochromocytoma), endocrine disorders (e.g., hyperthyroidism), neurologic disorders (e.g., stroke and Parkinson disease), vasomotor disorders, medications, and other disorders (e.g., heart failure and alcoholism). The exclusion of secondary causes was done by detailed history, physical examination, and if needed, laboratory investigation and radiological imaging.

PHH is identified according to the following diagnostic criteria: the presence of focal, visible excess sweating, with no apparent secondary causes, for at least 6 months in addition to the presence of at least two of the following: bilateral and symmetrical sweating; impairment of daily life activities; occurring at least once a week; the age of onset less than 25 years; positive family history; and absent during sleep.[5]

Informed consent was taken from each patient after which a detailed history and clinical examination were elicited in each case to exclude secondary causes of HH. When the secondary causes of HH were excluded and the patient was diagnosed as a case of PHH, a detailed history and cutaneous examination were done by a dermatologist with particular emphasis on HH and its effect on QoL. The history included demographic data (age, gender, occupation), site of HH, symmetry of HH, age of onset, family history, daily number of episodes, severity of HH according to HDSS, aggravating factors, seasonal variation, and whether HH stops during sleep or not. The thyroid function test was done for all the patients to exclude secondary causes related to thyroid metabolism. Then the patients were asked to fill out a 10-question questionnaire [Table 3], either electronically or on paper, according to patient preference. This questionnaire included the dermatology quality-of-life index (DLQI) with its Arabic translation.[27] Finally, the calculation of the DLQI score was done.

Table 3

DLQI questionnaire and its answers by patients

	Very much	A lot	A little	Not at all
1: Over the last week, how itchy, sore, painful, or stinging has your skin been?	8 (6%)	32 (22%)	27 (19%)	77 (53%)
2: Over the last week, how embarrassed or self-conscious have you been because of your skin?	33 (23%)	51 (36%)	25 (17%)	35 (24%)
3: Over the last week, how much has your skin interfered with you going shopping or looking after your home or garden?	22 (15%)	47 (33%)	29 (20%)	46 (32%)
4: Over the last week, how much has your skin influenced the clothes you wear?	48 (33%)	51 (36%)	20 (14%)	25 (17%)
5: Over the last week, how much has your skin affected any social or leisure activities?	14 (10%)	58 (40%)	36 (25%)	36 (25%)
6: Over the last week, how much has your skin made it difficult for you to do any sport?	20 (14%)	57 (40%)	23 (16%)	44 (30%)
7: Over the last week, has your skin prevented you from working or studying?	Yes: 88 (61%)		No: 56 (39%)
If “No,” over the last week how much has your skin been a problem at work or studying?		16/56 (28%)	31/56 (55%)	10/56 (17%)
8: Over the last week, how much has your skin created problems with your partner or any of your close friends or relatives?	3 (2%)	36 (25%)	28 (19%)	77 (54%)
9: Over the last week, how much has your skin caused any sexual difficulties?	11 (7%)	36 (25%)	14 (10%)	83 (57%)
10: Over the last week, how much of a problem has the treatment for your skin been, for example by making your home messy, or by taking up time?	6 (4%)	32 (22%)	26 (18%)	80 (56%)

Statistical analysis

Frequency (%) was used to describe categorical data. Mean and standard deviation were calculated to describe continuous data. Characteristics of PHH in affected patients can be found in Table 1. Statistical Product and Service Solutions (SPSS, V. 25) program was used for statistical analysis and the level of significance was set at (P < .05). Normality of distribution, tested using skewness and kurtosis of the curve in addition to the Shapiro–Wilk's test, was assumed for all the variables, and thus, parametric tests were used in the analysis. Independent Sample t-test [Table 2] was used to compare the age of onset of axillary, palmar, and plantar PHH, HHDS scale, and DLQI score among family history, gender, and different sites affected (axillary, palmar, and plantar). Equality of variances according to Levene's test was assumed. One-way analysis of variance (ANOVA) and Independent Sample t-tests were used to assess if there is a difference in age, age of onset of axillary, palmar, and plantar PHH, and the number of sites affected among HDSS (categorized into severe vs. mild-moderate) and DLQI (categorized into small to moderate effect vs. large effect vs. extremely large effect) variables. Analysis of covariance (ANCOVA) was used to assess the difference in age of onset among the family history variable after adjustment for severity.

Table 1

Characteristics of PHH in affected patients

Variable	Frequency	%	Mean	SD
Gender
Male	70	48.6%
Female	74	51.4%%
Age			26.6	7.2
Site
Axillary	90	62.5%
Palmar	78	54.2%
Plantar	62	43.1%
Craniofacial	11	7.6%
Genital	2	1.4%
Trunk	4	2.8%
Palmoplantar	62	43.1%
Palmoplantar and axillary	28	19.4%
Axillary only	53	37%
Palmoplantar only	31	22%
Number of affected sites
One site	73	50.7%
Two sites	40	27.8%
Three or more sites	31	21.5%
Age of onset (years)
Overall			14.5	5.1
Axillary			17.6	3.5
Palmar			11.6	4.2
Plantar			11.5	4.1
Craniofacial			18.1	6.2
Genital			18.0	1.4
Trunk			17.0	2.1
Family history	50	34.7%
Hyperhidrosis Disease Severity Scale			2.9	0.7
Mild or Moderate	44	30.6%
Severe	100	69.4%
DLQI			12.8	5.4
No effect at all on patient’s life	0	0%
Small effect on patient’s life (2-5)	13	9.0%
Moderate effect on patient’s life (6-10)	46	31.9%
Very large effect on patient’s life (11-20)	60	41.7%
Extremely large effect on patient’s life (21-30)	25	17.4%

Table 2

Independent Sample t-tests to compare age of onset, Hyperhidrosis Disease Severity Scale, and DLQI score among different variables

Variable	Level	Mean	P	Mean difference
Axillary age of onset
Family history	Not present	18.6	0.002	2.2
	present	16.3
Gender	Male	17.5	0.656	-0.3
	Female	17.8
Palmar age of onset
Family history	Not present	13.2	<.001	4.6
	Present	8.6
Gender	Male	12.4	0.189	1.31
	Female	11.1
Plantar age of onset
Family history	Not present	13.2	<.001	5.1
	Present	8.2
Gender	Male	11.9	0.444	0.81
	Female	11.2
Hyperhidrosis Disease Severity Scale
Family history	Not present	2.9	0.102	−0.21
	Present	3.1
Gender	Male	3.0	0.148	0.17
	Female	2.8
Axillary	Not present	2.9	0.500	−0.08
	Present	2.9
Palmar	Not present	2.7	0.000	−0.4
	Present	3.1
Plantar	Not present	2.8	0.003	−0.3
	Present	3.1
Number of sites affected	One site	2.7	0.001	−0.4
	Multiple sites	3.1
DLQI
Family history	Not present	12.4	0.164	−1.3
	Present	13.7
Gender	Male	13.1	0.635	0.4
	Female	12.6
Axillary	Not present	12.5	0.558	−0.5
	Present	13.1
Palmar	Not present	11.5	0.005	−2.5
	Present	14.0
Plantar	Not present	11.7	0.005	−2.5
	Present	14.3
Number of sites affected	One site	11.3	0.001	−2.9
	Multiple sites	14.3

Results

The prevalence of PHH in the Jordanian population was 3.2% (144 patients diagnosed with PHH out of 4,500 attendants who were surveyed), about half of them (n = 74, 51.4%) were females. The mean age was 26.6 ± 7.2 years, and the mean age of onset was 14.5 ± 5.1 years. The most affected sites were axillary (62.5%), palmar (54.2%), then plantar (43.1%) and the least affected sites were craniofacial (7.6%), trunk (2.8%), and genital (1.4%). About half of the patients had only one site affected, and the rest had two or more sites affected. All the patients had symmetrical HH except for two female patients where the right axilla was more affected than the left axilla. Palmar and plantar PHH were the first to appear at nearly 11½ years of age. Axillary, craniofacial, genital, and trunk PHH appeared later (at a mean age of 17–18 years). About one-third of the patients had a positive family history of PHH. Nearly 69% of the patients were severely affected according to the HHDS scale, while moderate HH was found in 31% of the patients with no cases of HDSS grade 1. Regarding the DLQI score, 31.9% were moderately affected, and 59.1% were severely affected. The average DLQI was 12.8 ± 5.5. More details can be found in Table 1.

The patients who had a family history of PHH were more likely to have axillary (mean difference [MD] =2.2 years, P = .002), or palmar (MD = 4.6 years, P < .001), or plantar PHH (MD = 5.1 years, P < .001) at an earlier age without any difference in severity according to HHDS (P = .102) or DLQI (P = .164). The difference remained significant after adjustment for severity. Moreover, there was no difference in age of onset or severity between males and females. There was no difference in severity according to HDSS (P = .500) or DLQI (P = .558) among patients with or without axillary PHH. The patients who had palmar PHH had more severe disease than patients without palmar PHH (HDSS MD = 0.418, P < .001; DLQI MD = 2.571, P = .005). In addition, patients who had plantar PHH had more severe disease than patients without plantar PHH (HDSS MD = 0.361, P = .003; DLQI mean difference = 2.591, P = .005). Multiple affected sites (two or more sites) were associated with higher severity (HDSS MD = 0.4, P = .001; DLQI MD = 2.9, P = .001) in comparison with one affected site. One-way ANOVA for HDSS (severe vs. mild-moderate) showed that mild to moderate patients are significantly (P = .025) older (mean = 28.68 years) than the severe group (mean = 25.7 years). No significant difference was there between the severe and non-severe groups regarding the age of onset of axillary (P = .387), palmar (P = .366), plantar (P = .487). Moreover, one-way ANOVA for DLQI (categorized as small to moderate effect vs. large effect vs. extremely large effect) showed that there was no significant difference between the groups regarding age (P = .431), age of onset of axillary (P = 0.790), palmar (P = .888), or plantar (P = .710).

The findings from our study affirm the broad effect of PHH on all areas of life including social and occupational life, emotional and physical impact, recreational activities, and sexual life. These effects can be clarified by analyzing the DLQI questionnaire [Table 3], which shows a high percentage of negative consequences on patient lives. PHH affected the choice of shoes and clothes in three-quarters of the patients. Sixty percent of the patients stated that PHH had affected their work or study. Social or leisure activity and sports were affected in 75% and 70% of the patients, respectively. Approximately 40% of the patients had sexual difficulties related to excess sweating, and nearly half of the patients had problems with family or close friends. More details regarding the effect of PHH on patients' lives can be found in Table 3. PHH and its harmful effects on QoL are underestimated by the patients and even by their primary care physicians. The majority of the patients (85%) did not consider PHH as a medical problem and therefore they did not seek any type of medical consultation for a long period of time. In addition, at the time the patient decided to seek medical help, half of the patients (52%) were told by their primary care physicians that this was a minor problem that did not necessitate any form of therapy or referral to other specialties.

Discussion

The prevalence of PHH in this study was 3.2% out of 4,500 patients who attended different outpatient clinics in JRMS hospitals. Axillary, palmar, and plantar PHH were the most common affected sites. Palmoplantar PHH appeared earlier than the other types. There are a few studies that discussed the prevalence of PHH and its effect on QoL, and to the best of our knowledge, there is no such study in Jordan or even in the whole Arab region.

The prevalence of PHH varies considerably in the literature, ranging from 0.93 to 14.7%.[11141516171819] The prevalence in our study was 3.2%, which is nearly similar to the studies done in Brazil by Westphal et al. (5.5%)[15] and Hasimoto et al. (0.93%)[17] and in China by Li et al. (4.36%).[16] Moreover, it was similar to what was found in the USA by Strutton et al. (2.8%)[11] and Doolittle et al. (4.8%).[18] Higher prevalence was found in Shanghai (14.5%) and Vancouver (12.3%)[19] among the dermatology outpatients, and in Brazil (14.76%) among medical students.[14] Extremely higher prevalence was found in India (38%),[28] Poland (16.7%),[29] and Germany (16.3%),[30] but we should take into consideration that the last three studies included primary as well as secondary HH cases. The possible reasons for this wide variation in PHH prevalence may include differences in methodology and diagnostic criteria of PHH used in these studies, different age groups, occupational and environmental factors in addition to variations in the genetic and ethnic backgrounds of the studied populations.

In our study, the males and females were equally affected, a majority of studies confirm this finding.[113132] Positive family history was found in 35% of the cases, similar to the studies done by Yamashita et al.[33] in Japan (36%), Felini et al.[31] in Brazil (44%), and Wadhawa et al.[34] in Nepal (47.7%), but lower than that observed by Ro et al. (65%).[20] Most studies in the literature found the axillary site to be the most frequent, followed by palmar, plantar, and craniofacial sites, which is similar to the results of our study.[35] Axillary HH was found in 65% of the American population affected by PHH,[18] similar to our findings (63%). In our study, 49% of the patients have two or more sites of involvement in concordance with the Nepalese population (51%).[34] The overall average age of onset was 14.5 years, similar to 13.2 years in a study done by Hasimoto et al.[17] In general, the age of onset was lower than 18–20 years in all the studies.[14183637] Severe HH (HDSS 3 or 4) presented in 69% of our patients, the same as in USA (70%),[18] but higher than Nepal (57%),[34] Japan (46.8%),[38] and Brazil (20.5%).[39] Palmar and plantar PHH age of onset was earlier than the other types of PHH, which is consistent with the findings from the USA.[40] We found that the severity of PHH is not related to gender, family history, or the age of onset. This issue has not been investigated previously in the literature. One possible explanation is that familial cases, that usually present earlier, result from different genetic variations and polymorphisms that phenotypically present with varying degrees of severity ranging from mild to severe.[41] Familial cases of axillary or palmar or plantar PHH presented earlier than non-familial cases, even after adjustment for severity, which is consistent with that observed in the USA.[40] Thus, earlier age of onset or presence of family history does not imply that PHH will be more severe. On the other hand, patients with palmoplantar PHH or with multiple affected sites had a more severe disease. This can be explained by the fact that palmoplantar localization leads to more impairment in daily life activities, and thus, increases the severity reported by patients. To the best of our knowledge, this association between the localization of PHH and severity has not been demonstrated before.

In our study, the average DLQI was 12.8, and the effect of PHH on the patient's QoL was large or extremely large in 65% of the patients. These findings were confirmed by multiple studies that reported a range of DLQI between 8.8 and 15 as well as more or less comparable results regarding the effect of PHH on different aspects of a patient's life.[1117262834424344] The average DLQI for PHH is comparable or even higher than that of multiple chronic dermatological diseases.[45464748] The average DLQI for PHH in our study was higher than all the dermatological diseases included in a study conducted in Saudi Arabia, except for papulosquamous disorders (DLQI = 15).[45]

These deleterious effects of PHH are underestimated by the physicians and even by the patients themselves. As a result, this disease remains underreported and underdiagnosed, which might exacerbate the condition even more.[18] Therefore, more awareness is needed to highlight this problem and its consequences, as well as, to educate patients about possible management options.

Conclusion

PHH prevalence among Jordanian patients attending the general outpatient clinics is 3.2%. Severe HH presented in nearly two-thirds of the patients, with the more severe disease being associated with plantar and palmar PHH in addition to having multiple affected sites. Our findings show that PHH has a negative impact on the QoL, affecting all aspects of a patient's life. The ultimate goal of this study is to improve the care of PHH patients by increasing physician and patient awareness of this disease, improving patient-doctor interaction, and addressing the patient's concerns.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Ethical approval

Institutional ethical approval was obtained from ethical committee (Approval # 4/2020).

Data availability statement

The dataset analyzed during the current study are available from the corresponding author upon reasonable request.

Financial support and sponsorship

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflicts of interest

There are no conflicts of interest.