In the present study, we found the prevalence of chronic scarring alopecia in Chinese SLE patients was 7.8%. Mucocutaneous lesions, high SLICC/ACR-DI and positive anti-Sm were risk factors for scarring alopecia, while renal and cardio-respiratory involvements and immunosuppressant treatment were significantly negative associated with it.
Hair loss is a frequent occurrence in SLE, divided as non-scarring and scarring alopecia. Discoid lupus erythematosus (DLE) is the typical clinical manifestation of chronic cutaneous lupus erythematosus, which is the only cutaneous lupus type healing with scarring . In early stage, DLE lesions present inflammatory infiltration. However, patients with scalp DLE proceed towards permanent and irreversible hair loss, once the replacement by fibrous tissue is established [14, 15]. The mechanism for the prevention of hair follicle regeneration and scarring occurring is still unknown. The localization of the hair follicle stem cells to the bulge area of hair follicle is one of explanation for this permanent hair loss process . The inflammatory aggregation in where high concentration of antigen-presenting Langerhans cells associated with hair follicle stem cells leads to the destruction of the sebaceous gland, causing collagenous transformation .
DLE happened in 11.2 to 17.6% SLE patients , and scarring alopecia has been reported happening in 34 to 35% DLE patients [9, 17]. However, the prevalence of scarring alopecia in SLE is seldom studied. The present study included 4792 SLE patients and demonstrated the prevalence of scarring alopecia 7.80%, which is consistent with a cross-sectional study from Korea . Although the prevalence for scarring alopecia is not that high, given its irreversible situation and reduced life quality of patients, we should learn the risk factors for scarring alopecia and try to prevent it from happening.
Smoking has been found an association with the prevalence or the activity of various autoimmune conditions . Additionally, skin manifestation in SLE has been revealed to be related to tobacco use . Moreover, smoking was found to worsen scalp DLE and make it resistant to treatment . In the present study, we found smoking could be a potential risk factor for scarring alopecia. Smoking cessation should be emphasized for SLE management and scarring alopecia prevention.
Anti-Smith (anti-Sm) antibodies are a highly specific autoantibody in SLE, directly against seven Smith proteins that constitute the small nuclear ribonucleoprotein particles [21, 22]. Besides acting as a SLE classification criterion, anti-Sm antibody has been found to be related with specific subsets of system involvements  and disease activity . In terms of skin manifestation, previous research revealed that anti-Sm antibody was associated with photosensitivity, malar rash, and discoid rash [25, 26]. Also, SLE patients with DLE had significantly increased anti-Sm antibody positivity than patients without DLE , which is consistent with our study that anti-Sm antibody served as a significant risk factor for scarring alopecia. However, the mechanism behind this association needs further research.
In terms of organ involvements, we found that mucocutaneous lesion was predictors for scarring alopecia, while renal and cardio-respiratory involvements were negatively associated with it. Previous studies indicated that DLE among SLE patients was a marker for less severe disease, with a significantly higher rate for cutaneous manifestations  and infrequently occurring in lupus nephritis and other severe organ involvements [27,28,29]. This was in keeping with our result, which indicated possible different molecular pathways for scarring alopecia and other major organ involvements in SLE patients. In addition, the less frequent severe organ involvement suggested that when effective and strong treatment strategies were adapted to the patients with life-threatening organ involvements, these patients were less likely to develop scarring alopecia.
Immunosuppressive therapies are recommended for severe organ-threatening or life-threatening SLE . Alopecia is a common side effect for immunosuppressive therapy, especially cyclophosphamide . However, the present study revealed that immunosuppressants were negative associated with scarring alopecia. The possible explanations are as followed. First, as mentioned above, patients with major organ involvements had less possibility to present scarring alopecia, so the more usage of immunosuppressive therapies, in some extent, explained this negative association. Second, in spite of the alopecia side effect of these immunosuppressants, these drugs have powerful efficiency in controlling the SLE disease activity and protecting major organ from threatening damage. Additionally, the present study showed that renal and cardio-respiratory involvements, which are indicators for vital systemic involvements, were negatively related to scarring alopecia, indicating the efficacy of immunosuppressive therapy in maintaining low disease activity to prevent scarring alopecia occurring.
Higher SLICC/ACR-DI was demonstrated in our cohort of SLE patients with scarring alopecia. Since we excluded the chronic scarring alopecia factor when calculating SCLICC/ACR-DI in regression analyses, this high score could be attributed to the other skin damages except for scarring alopecia and comorbid musculoskeletal damage. It was demonstrated in previous study that DLE patients had more damage accrual, particularly scarring alopecia, skin scarring, and skin ulcer , which explained the co-occurrences of scarring and other skin damages. In terms of musculoskeletal damage, high proportion of DLE patients was reported to have arthritis . However, different results were found in other studies that DLE was associated with reduced risk of arthritis [27, 28] or no association between alopecia and arthritis . In addition, muscle tenderness was revealed to be related with alopecia . To the best of our knowledge, no consensus was made in the association of musculoskeletal damage and scarring alopecia. In the present study, our results suggested that skin and musculoskeletal damages in SLE patients may share the same molecular pathways, which needs further investigation.
Some limitations of the present study should be addressed. First, this is a preliminary and exploratory case control study, lacking the record of the exact scarring alopecia occurrence time point, and the self-report questionnaires could cause bias to the ascertainment of scarring alopecia. Second, to our knowledge, this is the only study to present the prevalence and risk factors for scarring alopecia in SLE patients and was conducted only in Chinese SLE patients. The results should be verified in other SLE cohort population.