The concept of skin as a mirror of Parkinsonism dates back to the beginning of the last century. Since then, a good deal of evidence has been accumulated in support of the causal association between the neurological disturbance and changes detectable on areas of the integument with the richest sebaceous gland supply. SD is a common chronic and relapsing inflammatory skin disorder which primarily affects sebum rich areas. The prevalence of SD is 11.6% in USA  but can be higher in elderly people (over 80%)  and in Parkinsonism (52–59.5%) . In recent years, a few studies concerning SD and PD have been published [18–20]. To our best knowledge, this is the first culture-based epidemiology study performed on patients with SD and PD. In the present study male SDP was dominant and this was in agreement with the study carried out by Gupta who explained the observed result by stronger action of androgens in the male SD patients , as well as with the study by Wooten who found a male to female ratio in PD of 1.49 . Mean age of our SDP patients was 67 ± 7 years (Table 1) which was in agreement with studies restricted to individuals 65 years or above, confirming that the median incidence rate of PD was considerably higher in group above 60 year old .
The severity of SD depends on medical conditions and underlying diseases [13, 11]. Accordingly, we observed a high number of SDP with moderate or severe SD form and a high number of positive cultures (Table 2). Our data could be explained by predominant male gender and an increased level of SER and MSH secretion in PD patients .
Our culture-based study demonstrated six different Malassezia isolated in SDP patients, with M. globosa (42.3%) as the most dominant species (Figure 1). Several studies identified M. globosa as the most prevalent species in SD, suggesting its principal role in SD  but data for patients with PD have not been reported yet. By comparing the severity of SD and Malassezia presence on LS we did not find a significant difference between studied groups. By contrast, using the laboratory based quantitative test for Malassezia yeasts density (expressed as CFU/tape) we found more than twice higher CFU/tape for SDP/LS than SDN/LS group. Literature data are controversial; some studies showed that the density increases with the intensity of skin lesions, while other studies were unable to confirm this result . However, the reduction of Malassezia yeast density always results in SD outcome improvement .
The effects of the anti-Parkinson’s agent L-dopa on SD have been reportedly evaluated in Parkinson’s and data showed that treatment with L-dopa restores MHC-inhibiting factor synthesis and reduces sebum secretion in Parkinson’s . Our patients were treated with L-dopa during the course of this study so this can be reason for the similarity in the clinical findings between different groups, even high SD intensity in SDN group (Table 4). However, other factors contribute to SD development such as facial immobility (“mask-like face”) which may lead to an increased sebum accumulation.
The pathogenesis of SD is still not completely understood but some clinical studies indicated that Malassezia presence and replication plays a pivotal role. Positive clinical response of SD to antifungals (i.e., azoles, ciclopirox) could be explained by their role in reduction of Malassezia yeast proliferation, again confirming an important role of Malassezia density and infection in pathogenesis of SD.
Malassezia requires exogenous specific lipids for growth, therefore tends to appear on skin around the time of puberty, when there is an increase in androgens and consequently an elevation in sebum production . In patients with SD triglycerides and cholesterol are usually elevated but squalene and free fatty acids were significantly decreased compared to normal controls. Free fatty acids are formed from triglycerides through the action of bacterial lipases such as Propionibacterium acnes. This suggests that an imbalance of microbial flora and alterations in the composition of skin surface lipids may be involved .
Malassezia represents a part of human flora normally colonizing the skin surface but in some conditions it can change its saprophytic state and invade stratum corneum. Some culture-based laboratory studies identified differences between NLS and LS in the percentage of negative culture or in the presence and density of Malassezia. We did not find significant difference in the absence of Malassezia on NLS between HC and SDN, but very low number of negative Malassezia cultures was detected on NLS in SDP. It may suggest an important role of the host environment such as the SER in PD group which may provide favorable conditions for expressing higher virulence capacity of Malassezia. Recent study showed a possible role of lipase in the host environment to produce free fatty acids, which are important for enhancing the Malassezia virulence . The mechanisms of the Malassezia transition from commensal to pathogen are not clear yet, but this evidence is important for further studies due to the fact that lipases are further involved in the release of arachidonic acid, which can be important in cutaneous inflammation and disease .
It is well known that the development of infections depends on microbe’s replication while the severity of disease may depend of microbe’s enzyme production. In pathogenicity of SD phosphatase and lipase yeasts enzymes can initiate inflammatory response by releasing oleic and arahidonic acids from the sebum lipids [12, 28]. Fatty acids have direct irritant and desquamative effects on keratinocytes, while arahidonic acid metabolized by cyclooxigenase serves as a source of pro-inflammatory eicosanoides and leads to inflammation and damage to stratum corneum. Our strains tested for different enzymes classes’ expressed all type of phosphatase and lipase enzymes manly at a high level (Table 4). These findings suggest that the infection, yeasts replication and density are key pathogenic mechanisms in SD and can contribute to the development of Malassezia- driven pathogenic “vicious circle”, which closes due to the fact that saturated fatty acids, released by Malassezia lipase, are used as a “proliferative fuel” for these yeasts. M. globosa showed the highest lipase activity, suggesting that lipase could be a pathogenic factor in the skin diseases associated with different Malassezia and providing an explanation about M. globosa as the most important pathogenic species in PD patients with SD .
Literature data suggest the role of another mechanism in pathogenicity of SD. Beside infection the allergy host reaction to Malassezia antigens can be involved in SD. In atopic patients, some enzymes from protease and glycosidase classes, such as β–glucuronidase and leucine arylamidase, may act as antigens. Thus, genetic predisposition, as well as Malassezia antigens can lead to the local skin immune response and immunopathology and to development of SD [12, 29, 30]. In our study we clearly demonstrated very low impact of enzymes which may act as Malassezia antigens (Table 3).