Modifiable and non-modifiable epidemiological risk factors for acne, acne severity and acne scarring among Malaysian Chinese: a cross-sectional study

Acne vulgaris (henceforth acne) is a chronic inflammatory skin disorder with a multifactorial pathogenesis. It is the eighth most common skin disease worldwide, with the 2010 Global Burden of Disease Study estimating a global prevalence of acne (for all ages) of 9.38% [1]. However, in different countries and among different age groups, the prevalence of acne varies, with estimates ranging from 35% to close to 100% of adolescents having acne at some point [2]. Apart from the discomfort due to the clinical symptoms of acne, patients may experience other negative psychosocial impacts, like higher unemployment rates [3], increased depression and anxiety rates, lower self-esteem, and negative body image [4].

The pilosebaceous unit is well known as the site of acne development. The structure comprises the hair follicle and its connected sebaceous gland, which produces and secretes sebum onto the skin surface via the pore of the hair follicle [5]. Acne lesions develop when the pore of the pilosebaceous unit is blocked or inflamed [6]. The severity of acne is characterized by the number of non-inflammatory closed and open comedones, and inflammatory pustules, papules, and nodules. Cysts, scars, erythema and hyperpigmentation could also be present in more severe acne [6]. For this reason, acne may be present in a wide variety of clinical forms depending on the type, number, and severity of the predominant lesions, and could be categorised into different severity [7] and scarring [8] grades.

The most notable pathophysiological factors that influence the development of acne are increased Cutibacterium acnes colonisation of the follicle, sebaceous gland hyperplasia with seborrhoea, abnormal desquamation of sebaceous follicle epithelium (comedogenesis), and, moreover, inflammatory and immunological reactions [5]. Recently, we reviewed that epidemiological risk factors influencing acne presentation and severity include non-modifiable factors like positive genetic predisposition or familial history, and hormonal factors attributed to gender and age; and modifiable factors like lifestyle factors (smoking, alcohol, physical activity) and dietary habits of certain food types/groups [9].

While many epidemiology studies have investigated the risk factors for acne presentation, fewer studies have specifically studied the risk factors for acne severity and acne scarring. To date, Malaysian studies studying acne have only investigated the influence of dietary habits [10, 11], or the impact of acne on the quality of life [12, 13]. Therefore, this study investigated the prevalence of acne, acne severity and scarring grades, and their associated non-modifiable and modifiable epidemiological risk factors among Malaysian Chinese.

In the Malaysian Chinese studied, the prevalence of acne was 60.7%, lower than the prevalence among similar studies in Malaysia among Chinese adolescents (72.5% [12];) and medical students (68.1% [13];). The observed prevalence of moderate/severe acne (21.6%) and acne scarring (69.9%) was higher than the prevalence in previous Malaysian studies (9.8% [12]; and 9.3% [13]; for moderate/severe acne; 59% for acne scarring, [13]). Finally, while we did not find the male gender as a predisposing risk factor for acne presentation and severity unlike previous Malaysian studies [12, 13], we found that males had an increased risk for higher grades of acne scarring.

In this study, we found that those who had acne, regardless of severity and scarring grades, had strong positive familial history (either in parents and/or sibling). This proves that acne is a highly heritable trait. Recent genome-wide association studies (GWAS) and candidate gene association studies have identified that genetics, particularly gene variations, play a strong role in acne pathogenesis by modulating biological pathways like androgen metabolism, inflammation, stem cell fate and tissue remodelling (reviewed in [17]). Familial history did not show an additive effect for acne presentation; but for higher grades of acne scarring, maternal and paternal familial history showed stepwise, additive effects, while sibling history showed the opposite effect. However, in another Malaysian study, while maternal and paternal acne history significantly contributed to odds for developing acne (1.752 and 1.852, respectively), parental history showed an additive effect as the odds was increased to 3.056 [13]. Our recent meta-analysis found a pooled odds ratio of 2.91 (95% CI 2.58–3.28; familial history in parents with reference to no familial history in parents [9]); for acne presentation. However, the association between familial history and acne severity and scarring is unclear; some studies reported a higher prevalence of severe acne grade in those with a positive familial history of acne [18], while others did not [19‐21].

Dietary habits of certain food types/group seemed to decrease the risk for acne presentation, severity and scarring. Frequent consumption (most or all days) of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) decreased the risk for acne presentation and higher acne scarring, while periodic consumption (once/twice per week) of nuts and burgers/fast food decreased the risk for higher acne severity. This seems to indicate that having breakfast that is composed of those food components reduced acne presentation and higher scarring grade risks among Malaysian Chinese. In contrast, Ismail et al. [10] found that the consumption of milk ≥ once a week increased the risk of acne occurrence by 4 times (OR = 3.99, 95% CI =1.39–11.43) in a predominantly Malay Malaysian study, while Suppiah et al. [11] found that milk consumption was significantly higher (OR = 2.19, 95% CI = 1.04–4.65) among acne cases in a predominantly Chinese Malaysian study. The potential link between diet and acne presentation has been widely debated, with some studies finding no significant diet-acne link and others reporting that the intake of certain foods is associated with acne presentation (reviewed in [9]). For example, several studies found that frequent consumption of certain dairy products [22‐24], carbohydrates, high GI and glycaemic load (GL) diet [25‐27] is a potential risk factor for acne, which could be attributed partly to the insulin-like growth factor 1 (IGF1)/FoxO1/mTORC1 signalling pathway. Meanwhile, high adherence to a Mediterranean diet - characterised by an omega-3 rich, low-GI diet – was associated with a protective effect against acne, possibly by anti-inflammatory and anti-IGF1 mechanisms [28]. Probiotic use, either through topical or oral administration, has been shown to inhibit acne pathogenesis by directly inhibiting C. acnes through the production of antibacterial proteins or through anti-inflammatory immunomodulatory effects (reviewed in [29]). However, neither earlier Malaysian studies found significant association between yoghurt intake and acne risk [10, 11]. Taken together, since Jung et al. [30] showed that controls had higher regular breakfast intake compared to acne patients among Koreans, this indicates that regular breakfast intake - probably composing of butter, probiotic drink, cereals and milk as shown in this study - helps in reducing risk for acne presentation and higher acne scarring.

A few smoking variables – having a father who smokes, having at least one smoking parent and living in a household with at least one smoker – were associated with reduced risk of more severe acne in this Malaysian Chinese population. However, other smoking variables – personal smoking status and passive smoking – were not associated with acne severity, similar with an earlier Malaysian study [11]. We recently reviewed that the link between smoking and acne severity is controversial, with inconsistent results between studies [9]. Rombouts et al. [31] observed that smoking was linked to decreased acne risk in girls, while smoking was found to be a risk factor for acne [20] and severe acne occurred more frequently among smokers [32]. Studies also considered smoking duration and number of cigarettes smoked - one study observed a significant dose-dependent relationship between acne severity and the number of cigarettes smoked per day [33], another did not [31]. The complex way in which smoking influences the pathogenesis of acne including inflammation, wound healing and immune responses [31], may contribute, in part, to these inconclusive evidences.

In this study, we found that alcohol drinking was significantly associated with increased risk for acne presentation and higher grades of acne scarring, but the latter association was abolished after controlling for age and gender. In our recent review, alcohol intake is consistently not significantly associated with acne risk [9], as shown by majority negative previous findings [18, 33‐36].

BMI, sedentary lifestyle (assessed via computer/television usage), atopy, asthma, allergic rhinitis, eczema, atopic diseases and PCOS were not significantly associated with acne presentation in this Malaysian Chinese population. Nevertheless, being underweight was associated with increased risk of having higher grades of acne scarring, contrasting the findings of previous studies that reported higher acne prevalence in overweight individuals [18‐20, 37‐39]. However, an earlier Malaysian study found no significant association between BMI and acne presentation [10]. We also reported that having current asthma is a predisposing risk factor for higher grades of acne scarring, similar with the finding by Silverberg and Silverberg [40] which reported a significant association of severe acne with asthma.

Finally, age and household number were significantly associated with acne risk among Malaysian Chinese. Previous reports have observed highest acne prevalence among older teenagers and young adults and lower acne prevalence among older adults [41], which is in line with the results obtained in this study that demonstrate a higher risk of acne in those aged 20–24 relative to those > 24. None of the studies reviewed by us recently [9] investigated the association between household number and acne risk; thus, further studies are needed to understand the true relationship between the two.

We acknowledge a few limitations in our study. First, as the study subjects were Chinese university students and staff, the findings of this study could not be extrapolated to the multi-ethnic Malaysian population. Next, due to the retrospective cross-sectional study design used, it could only determine the differences within a population between those who have developed acne and those who have not. It was also only able to determine the association, but not the cause and effect of the modifiable risk factors on acne. Also, following the removal/addition of some list of foods in the questionnaire, we have not performed a reliability and validity calibration assessment. Nevertheless, removal/addition of foods is actually recommended by the original questionnaire designers in order to make it more relevant for a particular country [14]. Apart from the three-level food frequency questionnaire used in this study, more frequency levels, more commonly-consumed food types, or even a repeated three-day food dairy (two weekdays and one weekend) could be adopted. Other psychosocial factors contributing to - or impacted from acne - like quality of life [12, 13], stress, depression, anxiety, and sleep quality, could be taken into account in future studies. Despite these limitations - with sample size of almost 2000 subjects – we have evaluated a wide range of epidemiological risk factors and encompassing not just acne presentation, but also severity and scarring. The findings of from our study have provided further support to the existing evidence for the role of familial history and dietary habits in acne occurrence.

In conclusion, positive familial history is a strong predisposing factor in influencing acne presentation, severity and scarring among Malaysian Chinese. Frequent consumption of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) is protective against presenting with acne and having higher acne scarring grades, while alcohol drinking habit is a predisposing risk factor for acne among Malaysian Chinese. The predisposing risk factors revealed in this study can help researchers and clinicians to understand the epidemiology and pathophysiology of acne, and hence develop effective interventions especially targeting modifiable factors like dietary habits and lifestyle factors.