Quantifying the Association Between Anxiety and Depressive Features and High Disease Activity Scores in SLE

Anxiety and depression can limit engagement with healthcare or treatment leading to later diagnosis, poor treatment adherence, and poor disease control with associated negative sequelae.

Anxiety and depression are 2 of the most common conditions encountered by budding physicians irrespective of their primary specialty. Within rheumatology, these conditions can negatively impact the patient experience at several junctures. They can limit engagement with healthcare or treatment leading to later diagnosis, poor treatment adherence, and resultant poor disease control with associated negative sequelae. The clinical presentation of anxiety and depression can also overlap with features of active rheumatic disease, exacerbating the symptom burden experienced by patients.1 Within the paradigm of systemic lupus erythematosus (SLE), fatigue symptoms can be more prominent and can worsen with a coexistent diagnosis of depression.2 Furthermore, poorly treated depression and anxiety features can become a significant confounder when assessing outcome measures such as the Visual Analogue Scales (VAS), Short Form 36, FACIT-Fatigue, and other patient reported outcome scores.3

A recent Chinese observational single center cross-sectional study assessed the impact of SLE disease activity on the prevalence of anxiety or depressive features.4 This study enrolled 325 patients over the age of 18 with SLE as defined by the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Key exclusion criteria were a previous diagnosis of anxiety/depression or other psychiatric illness, major organ pathology, and those with a history of substance abuse. Depressive features were assessed using the Patient Health Questionnaire 9 (PHQ-9) and anxiety features were assessed using the 7 item General Anxiety Disorders Scale (GAD-7). SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI).

Within the 325 patients enrolled to the study, 61.5% had a PHQ-9 score compatible with significant depression and 54.4% had a GAD-7 score compatible with significant anxiety. Patients with significant depressive/anxiety features had significantly higher SLEDAI scores than their counterparts (p=0.001) and had significantly higher rates of musculoskeletal and neuropsychiatric involvement. This is concordant with previous work which has shown musculoskeletal features to be key drivers of the patient experience in SLE.5

Key confounders were mostly similar between the anxiety/depression and non-anxiety/depression groups except for household income. Those with a low household income defined as >50,000 Renminbi (RMB) had higher rates of depression than those with a higher income (p=0.005).

The authors used receiver operating characteristic (ROC) curve analysis to assess the utility of SLEDAI as a predictor of depression or anxiety in SLE patients. The optimal cut-off of SLEDAI >8.5 demonstrated a sensitivity of 50.5% and specificity of 78.4% in predicting depression (AUC 0.660, p <0.001). This cut-off had a sensitivity of 54.2% and specificity of 78.4% in predicting significant anxiety (AUC 0.684, p <0.001).

There are several limitations to this study; the authors identify the lack of longitudinal data as a key factor. The lack of ethnic diversity within the cohort is another important consideration. As with most SLE research, the chosen disease activity score has several additional limitations. SLEDAI scores features such as arthritis, rash, and oral ulceration based on the presence or absence of these features. Therefore, a patient with a severe rash encompassing >50% of their body surface area scores the same as one with a mild malar rash. Additionally, a patient with 2 synovitic joints scores the same as one with 12 synovitic joints, despite their very different clinical presentation. Therefore, the use of an alternative measurement such as the British Isles Lupus Assessment Group (BILAG-2004) score might allow for greater fidelity when describing a patient’s individual symptom burden.6 Exclusion of those with a pre-existing diagnosis of anxiety/depression in this study is understandable but given the widespread prevalence of these diagnoses, it may limit the generalizability of these findings in the rheumatology clinic.

This study does provide welcome data on an underappreciated and often poorly addressed feature of long term SLE management. The association between high disease activity and worsening depressive/anxiety features would seem obvious; however, this paper provides welcome quantitative evidence to the fact. Holistic care in SLE is critical and the mental health sequelae of high disease activity require addressing in a similar manner to the musculoskeletal or mucocutaneous features.


1. Arnaud L, Mertz P, Amoura Z, Voll RE, Schwarting A, Maurier F, et al. Patterns of fatigue and association with disease activity and clinical manifestations in systemic lupus erythematosus. Rheumatology [Internet]. 2021 Jun 18 [cited 2021 Jul 7];60(6):2672–7. Available from: https://pubmed.ncbi.nlm.nih.gov/33175957/

2. Figueiredo-Braga M, Cornaby C, Cortez A, Bernardes M, Terroso G, Figueiredo M, et al. Depression and anxiety in systemic lupus erythematosus: The crosstalk between immunological, clinical, and psychosocial factors. Medicine (Baltimore) [Internet]. 2018 Jul 1 [cited 2023 Jan 17];97(28). Available from: /pmc/articles/PMC6076116/

3. Meacock R, Dale N, Harrison MJ. The humanistic and economic burden of systemic lupus erythematosus: A systematic review [Internet]. Vol. 31, PharmacoEconomics. Springer; 2013 [cited 2021 Jul 2]. p. 49–61. Available from: https://link.springer.com/article/10.1007/s40273-012-0007-4

4. Liao J, Kang J, Li F, Li Q, Wang J, Tang Q, et al. A cross-sectional study on the association of anxiety and depression with the disease activity of systemic lupus erythematosus. BMC Psychiatry [Internet]. 2022 Dec 1 [cited 2022 Oct 6];22(1):591. Available from: https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-04236-z

5. Chaigne B, Chizzolini C, Perneger T, Trendelenburg M, Huynh-Do U, Dayer E, et al. Impact of disease activity on health-related quality of life in systemic lupus erythematosus - a cross-sectional analysis of the Swiss Systemic Lupus Erythematosus Cohort Study (SSCS). BMC Immunol [Internet]. 2017 Mar 28 [cited 2022 Mar 18];18(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28351341/

6. Carter LM, Gordon C, Yee CS, Bruce I, Isenberg D, Skeoch S, et al. Easy-BILAG: a new tool for simplified recording of SLE disease activity using BILAG-2004 index. Rheumatology (Oxford) [Internet]. 2022 Oct 6 [cited 2023 Jan 17];61(10):4006. Available from: /pmc/articles/PMC9536795/