Headaches in SLE patients: a cross-sectional analysis of clinical, immunological, and Radiological Correlations

Abstract

Background

Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations, including a significant prevalence of headaches. This cross-sectional study aimed to thoroughly explore the relationship between SLE and headaches by analysing their prevalence, types, and associated clinical, immunological, and radiological factors.

Method

A comparative analysis was conducted on 179 SLE patients, who were categorized into two groups: those with headaches and those without. Data collection encompassed demographic details, disease activity levels, neurological assessments, immunological profiles, and brain imaging results. Headaches were diagnosed and classified following the International Classification of Headache Disorders (ICHD-3). Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Statistical analyses were performed to identify significant associations and correlations.

Results

Headaches were observed in 55% of the SLE patients, predominantly presenting as tension-type headaches (65%) and migraines (27%). Notably, no patients met the criteria for a lupus-specific headache. The Headache Group exhibited significantly higher disease activity (SLEDAI scores). Tension-type and migraine headaches were particularly associated with increased muco-cutaneous manifestations. The presence of antiphospholipid (aPL) antibodies was significantly linked to migraines and cluster headaches. While neurological disorders such as ischemic stroke and venous sinus thrombosis were more prevalent in the Headache Group, these findings were not statistically significant. Brain MRI abnormalities were detected in 9.4% of patients with headaches, including venous sinus thrombosis (2.3%), ischemic stroke (5.8%), and white matter hyperintensities (1.1%).

Conclusion

This study underscore es the complex relationship between SLE and headaches, suggesting that headaches may serve as an indicator of heightened SLE disease activity. Immunological factors, particularly aPL antibodies, show a strong association with specific headache types. MRI abnormalities further emphasize the intricate neurobiological aspects in SLE patients experiencing headaches. Continued research is essential to better understand biomarkers, genetic factors, and effective treatment strategies for managing headaches in SLE patients.

Introduction

Systemic Lupus Erythematosus (SLE), a complex autoimmune disorder, presents with a wide range of clinical manifestations, among which headaches are particularly multifaceted [1]. The intricate relationship between SLE and headaches has become a key area of research, especially given the high prevalence of migraines among SLE patients [2, 3]. Various studies have investigated the prevalence of different headache types in SLE, including tension-type headaches, migraines, cluster headaches, and headaches related to increased intracranial tension (ICT) [4, 5]. The diverse findings across these studies highlight the complexity of the immune system’s involvement in the development of headaches in SLE.

Neuropsychiatric manifestations such as ischemic stroke and venous sinus thrombosis have been observed in SLE patients experiencing headaches, though the consistent clinical significance of these findings remains an ongoing subject of research [3, 5]. To gain a comprehensive understanding, comparative studies, like that of Katsiari et al. (2011), have contextualized headaches in SLE by comparing them to those in other autoimmune conditions, such as multiple sclerosis, emphasizing the importance of examining headaches within the broader spectrum of autoimmune disorders [3].

Our study seeks to provide detailed insights into the various dimensions of headaches in the context of SLE. Several underexplored aspects represent a research gap in this area: the mechanisms linking headaches to SLE activity, particularly the role of the immune system, remain unclear; longitudinal studies are necessary to track the progression of headaches in SLE patients over time; comparative analyses should further distinguish SLE-related headaches from those in other autoimmune conditions; the clinical significance of the association between antiphospholipid (aPL) antibodies and specific headache types requires deeper investigation, as does the potential for headaches to serve as early indicators of severe neuropsychiatric complications. Additionally, the relevance of MRI abnormalities in SLE patients with headaches warrants further exploration. Addressing these gaps could significantly enhance our understanding of headaches in SLE.

Methods

A comparative cross-sectional study was conducted, involving 179 Systemic Lupus Erythematosus (SLE) patients aged 18 to 55, who met the 2012 Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria for SLE [6]. The participants were selected from the rheumatology & immunology unit outpatient clinic at our institution between July 2022 and July 2023. The patients were categorized into two groups: Group I (SLE with Headache) and Group II (SLE without headache).

Exclusion criteria encompassed patients with any medical disorders not related to lupus, including other systemic autoimmune diseases, hereditary neurological disorders, and primary epilepsy, as these conditions could confound the neurological assessments and headache classification.

Demographic data, including age and gender, were collected. A thorough medical history was obtained, detailing the main clinical features, followed by a clinical examination by an experienced internist (EH) and a neurological examination by an experienced neurologist (ABT). Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [7].

Patients’ sera were screened for positivity in antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies, and Antiphospholipid Antibodies (aPL). Additionally, a complete blood count, creatinine, and urinary protein/creatinine ratio measurements were conducted for all participants. Fundus examinations were performed on all patients.

The presence of headache was identified through an initial question regarding headaches within the past year, including the frequency and number of headache attacks. This information was crucial for evaluating the significance of headache characteristics in relation to the study’s results.

Headaches were diagnosed and classified according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) [8], covering four primary headache types: migraine, tension-type headache (TTH), cluster headache, and secondary headaches such as those from idiopathic intracranial hypertension (IIH). IIH is characterized by moderate to severe headache, often with a pulsating quality, typically aggravated by straining (such as with coughing or bending over), and may be associated with nausea, vomiting, and visual disturbances. Diagnosis is based on specific criteria, including elevated intracranial pressure, normal neuroimaging (except for empty sella), and the absence of other underlying causes.

“Lupus headache” is one of the items in the SLEDAI-2 and has been defined as a severe, disabling, persistent headache that is not responsive to narcotic analgesics [9]. Headache severity was measured using the Visual Analog Scale (VAS) [10], recorded by a mark on a 10 cm line ranging from “no pain” to “worst possible pain.”

CT, MRI, MRV, and MRA brain imaging were performed when indicated based on clinical presentation, such as the presence of neurological deficits, severe or atypical headache patterns, or suspicion of secondary causes of headaches.

The study adhered to ethical standards, obtaining informed consent from all patients and controls following the local ethical committee guidelines. The study was performed in accordance with the Declaration of Helsinki and was approved by the ethical committee of our institution in February 2023 (Reference number: INTM 13 − 2).

Data analysis was performed using SPSS software version 20 (IBM Corp, Armonk, New York, United States). Continuous variables were presented as mean ± standard deviation (SD). One-way ANOVA was employed for normally distributed data, while the Kruskal-Wallis test was used for non-normally distributed data. Qualitative variables were expressed as numbers and percentages, analysed using Chi-square or Fisher’s exact test. Correlation between variables was assessed using the Spearman coefficient. The significance level was set at P < 0.05.

Results

A total of 179 patients diagnosed with Systemic Lupus Erythematosus (SLE) were included in the study, with a predominance of females (162, 90.5%) compared to males (17, 9.94%). The female-to-male ratio was 9.5:1. SLE patients were categorized into two groups: Headache Group I (100 patients) and Non-Headache Group II (79 patients). The groups demonstrated comparability in terms of age, sex, and disease duration. No statistically significant differences were observed in clinical presentation and laboratory investigations between the two groups [Table 1].

A significant statistical difference was noted in disease activity between the two groups, with headache sufferers exhibiting a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p < 0.0001) [Table 1].

Table 1 Demography, clinical and laboratory data of the studied SLE patients

Among SLE patients with headaches (n = 100), 55.86% experienced primary headaches. Tension-type headache (TTH) was the most common type (65%), followed by migraine (27%). Notably, 5% of patients had headaches related to increased intracranial tension (ICT), which are classified as secondary headaches. The causes of ICT headaches among these patients included idiopathic intracranial hypertension (IIH), as there were no cases of space-occupying lesions such as brain tumors or brain abscesses. None of the patients met the SLEDAI criteria for lupus headache, and no patients experienced more than one type of headache simultaneously.

Approximately one-third of lupus patients experienced headaches prior to their lupus symptoms. Among them, 63% reported headaches lasting from over one to five years before diagnosis, while 37% experienced headaches for less than a year. Headaches were categorized as follows: 50% migraine with aura, 16.7% idiopathic intracranial hypertension (IIH), and 33.3% tension-type headaches (TTH). Half of these patients had a family history of headaches, predominantly migraines (90%) and 10% TTH. 60% had a headache history of 1–5 years, with 35% experiencing daily headaches. Headache duration without medication was: <1 h (48%), 1–4 h (21%), > 4 h (31%). With medication, 73% had headaches < 1 h, 10% for 1–4 h, and 12% >4 h [Table 2].

Headache triggers included stress (75%), fatigue (5%), menstruation (5%), dietary factors (3%), sleep deprivation (2%), and other factors (10%). During lupus exacerbations, 32% reported worsened headaches. Pregnancy exacerbated headaches in 15% but improved them in 10% of patients. Regarding seasonal variations, 88% reported no changes, 7% increased headaches in summer, and 5% in winter. Steroid use for lupus exacerbation improved headaches in only 4% of patients [Table 2].

Statistical analysis revealed a significant association between headache type and mucocutaneous manifestations. Tension-type headache (TTH) and migraine were linked to higher occurrences of mucocutaneous manifestations. Additionally, Antiphospholipid (aPL) antibody positivity showed a statistically significant association with migraine and cluster headache (70.5% in migraine vs. 100% in cluster headache, vs. 16.9% in TTH, 20% in the IIH group, p < 0.000) [Table 3].

Table 2 Headache characteristics and modifying factors in the studied patients

Table 3 Relation of headache to clinical and laboratory data

Neurological disorders, specifically ischemic stroke (5/100) followed by venous sinus thrombosis (2/100), were more prevalent in the headache groups. These conditions are often associated with the hypercoagulable state linked to antiphospholipid syndrome or vasculitis in SLE patients. Nearly all the 7 patients with ischemic stroke and venous sinus thrombosis had seizures at presentation. Lupus headache was not included in this study, as none of our patients had a headache that met the criteria for lupus headache.

MRI brain results indicated that 90.6% of headache sufferers (from a total of 85 patients who underwent MRI) had a normal MRI, while the remaining 9.4% showed abnormalities, including venous sinus thrombosis in 2 patients (2.3%), ischemic stroke in 5 patients (5.8%), and white matter hyperintensities in 1 patient (1.1%). The two patients who had venous sinus thrombosis on MRI had history of tension-type headaches. Of the ischemic stroke patients, four had a history of migraines, and one had a history of tension-type headaches. The patient with white matter hyperintensities had a migraine headache. Notably, all patients with cluster headaches had normal MRI findings. Two of the patients without headaches had ischemic stroke (2.5%) [Figs. 1, 2 and 3].

Fig. 1

25y female with SLE for 2 years presented with tension like headache, blurring of vision, repeated vomiting, fundus exam shows grade II papilledema, MRV show left transverse and sigmoid venous sinus thrombosis

Fig. 2

32y, male, SLE for 4 years, presented with sudden onset left sided numbness with MRI brain DWI (A) show restricted diffusion and FLAIR (B) show hyperintense signals of Right parietal cortical and subcortical areas denoting recent infarction

Fig. 3

30y female, SLE for 5 years with history of migraine 1y before lupus diagnosis, with MRI FLAIR show scattered foci of small white matter hyper intensities (WMH) concomitant with migraine

The severity of headaches, as measured by the Visual Analog Scale (VAS), correlated with SLEDAI but did not reach clinical significance. No statistically significant difference was found between headache type and SLEDAI [Tables 4 and 5].

Table 4 Distribution of headache types across SLEDAI scores in SLE patients

Table 5 Correlation of SLEDAI & VAS

In the multivariate regression analysis examining the relationship between headaches and various factors, the intercept is highly significant, indicating a baseline likelihood of headaches when all other variables are zero. The SLEDAI score is also highly significant, showing that higher disease activity is strongly associated with an increased likelihood of headaches. Conversely, renal symptoms significantly reduce the likelihood of headaches. However, other factors, including age, sex, duration of the condition, mucocutaneous symptoms, arthritis, serositis, neuropsychiatric symptoms, anti-DNA antibodies, and antiphospholipid antibodies, do not show significant associations with headaches. Issues with the data for ANA and anti-DNA antibodies suggest that these variables may need further review. Overall, the SLEDAI score stands out as the most significant predictor of headache occurrence in this analysis [Table 6].

Table 6 Multivariate regression analysis between headaches and clinical SLE variables

Discussion

Our comparative cross-sectional study advances the current understanding of the intricate relationship between SLE and headaches, integrating insights from various studies that explore different facets of this association [3,4,5, 10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28] [Table 7].

Table 7 Baseline characteristics of published studies investigating headache in systemic lupus erythematosus (SLE) patients: correlations with MRI and immunological investigations (1982–2023)

The prevalence of headaches in SLE patients, ranging from 28.5 to 82% in previous studies [3,4,5, 10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28], aligns with our findings, where headaches were observed in 55% of our SLE cohort.

The prevalence of headaches in Egyptian patients with systemic lupus erythematosus (SLE) varies across studies from 55 to 38% [4, 28,29,30,31,32,33,34,35].

This significant variance in prevalence among studies can be attributed to methodological differences, varying patient numbers, and widely differing criteria for defining headache types. Despite observing a female predominance in our SLE cohort, consistent with established epidemiological patterns, we found no significant differences in age, sex distribution, or disease duration between SLE patients with and without headaches.

In a related study focusing on childhood SLE, Santos et al. examined a population of 1,463 SLE patients, revealing that 29.9% experienced 869 neuropsychiatric SLE events, averaging 2.48 events per patient. Headache was reported in 52.2% of these cases [27]. However, it is noteworthy that a meta-analysis conducted by Mitsikostas et al. presents a contrasting perspective. Pooled data from seven controlled studies in their analysis showed that the prevalence of all headache types, including migraine, did not differ significantly from controls [17].

Regarding headache subtypes, migraines (27%) and tension-type headaches (65%) emerged as the predominant subtypes, consistent with existing literature. None of our patients were found to have lupus headaches, in agreement with other studies where it was 1.5% in the study by Hanly et al. [22], and none in the study by Aloleimy et al. [4]. This questions the existence and clinical significance of lupus headache, emphasizing the need for a standardized classification system for lupus-related headaches to enhance diagnostic precision, as the available evidence does not strongly support the concept of a distinct entity known as ‘lupus headache.

Our finding that 55% of SLE patients experience headaches, predominantly tension-type and migraine, contributes new data to the existing literature. Unlike previous studies that have reported varying prevalences, our study provides a detailed breakdown of headache types and their association with disease activity. Notably, none of our patients met the criteria for lupus-specific headaches. This absence challenges the clinical relevance of this classification, highlighting the need for a standardized diagnostic approach. This finding is crucial as it questions the concept of ‘lupus headache’ and suggests that such a classification may not be clinically significant.

In recent decades, researchers have explored the intersection of migraines and immunological/autoimmune disorders due to substantial evidence linking both conditions. Epidemiologically, both conditions predominantly affect females, with an onset typically at young ages [36, 37]. Pathologically, shared genetic components, particularly involving human leukocyte antigens (HLA) and cytokine polymorphisms [37], establish a connection between migraine pathogenesis and autoimmune disorders. This association is further underscored by elevated levels of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IL-8 in migraines, indicative of a persistent pro-inflammatory environment [38]. Notably, during migraine attacks, there is an increase in IL-10 levels, suggesting a compensatory anti-nociceptive response [39]. Additionally, immune cell subset al.terations, involving natural killer cells, as well as CD4 + and CD8 + lymphocytes [40], hint at potential dysregulation contributing to the underlying pathophysiology of migraines.

Regarding lupus headache, its pathophysiology appears to involve two primary pathways. The ischemic-vascular mechanism involves antiphospholipid antibodies (aPL), immune complexes, and leuko-agglutination, contributing to focal neuropsychiatric manifestations. The inflammatory-neurotoxic mechanism includes complement activation, increased blood-brain barrier permeability, migration of intrathecal autoantibodies, and local production of pro-inflammatory cytokines, associated with diffuse neuropsychiatric manifestations [41].

Shifting focus to tension-type headaches, although they have received limited attention in terms of immune system derangement, there are indications of increased pro-inflammatory cytokines, particularly in the cerebrospinal fluid [42]. For cluster headaches, there is also evidence suggesting a role for immunological dysfunctions in the pathogenesis of this disorder, indicated by a negative association with HLA-B14, an increase in natural killer (NK) cytotoxicity, elevated receptor expression of classical neurotransmitters associated with pain, and elevated levels of pro-inflammatory cytokines such as IL-1β [43].

There appears to be an association between idiopathic intracranial hypertension (IIH) and systemic lupus erythematosus (SLE), although the exact relationship is not fully understood. IIH has been recognized as a complication in SLE, with a prevalence ranging from 0.7 to 1.5%. However, it remains an uncommon manifestation of SLE. IIH can occur as the initial presentation of SLE, even in the absence of other systemic symptoms. In one study, 17% of lupus patients with intractable headaches were found to have IIH on CSF studies. The pathophysiology linking IIH and SLE is unclear. Proposed mechanisms include immune-mediated injury within the arachnoid villi, disruption of the blood-brain barrier, and abnormal regulation of CSF production. Antiphospholipid antibodies may also play a role. Treatment of the underlying SLE with corticosteroids and immunosuppressants like cyclophosphamide has been effective in resolving IIH in some cases. However, more research is needed to establish optimal treatment guidelines [44, 45].

We noted that headache sufferers exhibited a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score compared to SLE patients without headaches (p < 0.0001). This finding is consistent with the conclusions drawn by Appenzeller et al. (2004), where migraines in SLE patients were linked to elevated MEX-SLEDAI scores [16]. Additionally, multivariate regression analysis revealed a strong link between the SLEDAI score and headache likelihood. This association highlights the potential clinical relevance of headaches as a marker for increased SLE disease activity.

Despite the lack of a significant correlation between headache severity and disease activity assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), our findings are consistent with those reported by Katsiari et al. (2011) and other researchers [3,4,5, 11,12,13,14]. Unexpectedly, our investigation did not uncover a substantial link between the existence of headaches and specific clinical manifestations. This finding contradicts certain studies that highlighted musculoskeletal and neuropsychiatric manifestations as prevalent in individuals experiencing headaches [4]. On the other hand, there was a notable correlation between migraine and tension-type headaches and mucocutaneous manifestations. Notably, Appenzeller identified a significant association between migraines and Raynaud’s phenomenon as well as organ damage [16].

Additionally, aPL antibody positivity showed a statistically significant association with migraines and cluster headaches. Our findings are consistent with prior research that underscores the potential involvement of anti-phospholipid (aPL) antibodies in SLE-related headaches [4], aligning with previous studies that explored the role of autoantibodies in neuropsychiatric manifestations. Faust et al.‘s investigation into neurotoxic lupus autoantibodies [46], and Toubi and Shoenfeld’s identification of the association of anti-P antibodies with neuropsychiatric symptoms [47], offer compelling evidence of a direct immunological link between SLE and neurological dysfunction. Yoshio et al.‘s focus on IgG anti-NR2 glutamate receptor autoantibodies add another layer to our understanding, connecting inflammatory processes to neurological symptoms, including headaches [48].

In Fragoso-Loyo’s study, patients with headaches displayed elevated cerebrospinal fluid (CSF) levels of IL-6, IL-8, IP-10, RANTES, and MIG compared to non-NPSLE and non-autoimmune disease patients [49]. Autoantibodies, such as anti-ribosomal-P, anti-DNA/NR2, antiphospholipid (aPL), and anticardiolipin (aCL), significantly contribute to neuropsychiatric systemic lupus erythematosus (NPSLE), contributing to neurotoxicity and blood-brain barrier (BBB) dysfunction [41]. Notably, associations of autoantibodies to β2-glycoprotein I (β2GPI) with non-specific intractable headaches, ischemic stroke, and seizures in NPSLE patients suggest their potential to surpass the predictive value of other autoantibodies like aCL or lupus anticoagulant [50].

Our study underscores the significant association between antiphospholipid (aPL) antibodies and specific headache types, particularly migraines and cluster headaches. This adds to the growing body of evidence linking autoimmunity and headache pathogenesis. The association with higher SLE disease activity scores in patients with headaches further supports the role of headaches as a potential marker for increased disease severity.

In our patient cohort, nearly 92% exhibited no abnormalities in brain MRI scans. Consistent with findings from other studies [1], we did not observe any significant association between cerebral lesions and headache characteristics, including types. Nevertheless, our investigation identified ischemic stroke followed by cerebral venous thrombosis as the primary MRI abnormalities. Both cases of CVT were associated with TTH, and 4/5 cases with ischemic stroke were migrainous. Only one case had hyperintensities on MRI.

Several studies have explored brain imaging findings in SLE patients, providing valuable insights. Nobili et al. (2006) noted focal hypoperfusion in 83% of SLE patients with migraines using brain SPECT [51]. Bicakci et al. (2008) established a correlation between abnormal MRI findings and prolonged disease duration, suggesting progressive neurological involvement in SLE [20]. In a study by Sarbu et al. (2015), brain abnormalities were identified in 59.3% of neuropsychiatric lupus patients, with small vessel disease predominantly correlated with lupus anticoagulant [24]. Zaky et al. (2015) reported brain abnormalities in 38.2% of SLE patients, with those diagnosed with NPSLE showing higher frequencies of white matter changes, ischemia, hemorrhage, and encephalopathy [52]. Tjensvoll et al. (2016) associated migraines in SLE with reduced cerebral grey matter volume [25], while Son et al. (2016) linked chronic daily headaches in SLE with neuronal dysfunction and neurometabolic changes [53]. Papadaki et al. (2018) explored cerebral perfusion abnormalities using perfusion-weighted MRI, emphasizing cerebral hypoperfusion in SLE patients with headaches and suggesting a potential vascular component [26]. A recent study by Aloleimy et al. (2021) found brain imaging abnormalities in 25.8% of patients, with white matter hyperintensities being the most frequent pathology [4].

The MRI findings in SLE patients with headaches highlight a convergence of structural, vascular, and immunologic aspects which can be explained by various molecular mechanisms. In approximately 30–40% of SLE patients, autoantibodies target the NR2A/B subunit of the NMDA receptor, leading to neuronal apoptosis and hippocampal damage, as demonstrated in both in vitro and animal models [54].

Additionally, matrix metalloproteinases (MMPs), especially MMP-9, play a crucial role in degrading extracellular matrix components, which compromises the integrity of the blood-brain barrier (BBB) in neuropsychiatric SLE (NPSLE). Elevated levels of MMP-9 in the serum and cerebrospinal fluid (CSF) of NPSLE patients are associated with neurodegenerative markers, indicating its role in BBB disruption and central nervous system (CNS) involvement [55].

Furthermore, neutrophils in SLE exhibit increased granulopoiesis and enhanced formation of neutrophil extracellular traps (NETs), characterized by the release of histones and enzymes such as MMP-9. This contributes to heightened intravascular activation, cell death, and an exacerbated inflammatory response in NPSLE [56]. Concurrently, pro-inflammatory cytokines like IL-1, IL-6, and IFN-γ, produced by neurons and microglia, further intensify this response. Notably, elevated IL-6 levels in the CSF are associated with abnormal brain MRI signals and blood-brain barrier (BBB) dysfunction, fueling the inflammatory cascade that drives many of the neurological manifestations observed in NPSLE [57].

The management of headaches in Systemic Lupus Erythematosus (SLE) patients requires a nuanced approach, considering both the underlying autoimmune disease and the specific type of headache experienced. For primary headaches such as migraines and tension-type headaches, standard treatments are generally employed. Migraine management often includes triptans, such as sumatriptan, and preventive medications like beta-blockers, amitriptyline, or topiramate, tailored to the severity and frequency of the attacks [58]. Tension-type headaches may benefit from over-the-counter analgesics like ibuprofen or acetaminophen, with chronic cases potentially requiring tricyclic antidepressants (TCA) or other prophylactic agents [59]. For headaches associated with secondary causes like antiphospholipid syndrome or cerebrovascular events, addressing the underlying condition with anticoagulants or other specific therapies is crucial [60]. Overall, a multidisciplinary approach involving rheumatologists and neurologists is often required to tailor headache management to the unique needs of SLE patients, balancing efficacy and safety while minimizing drug interactions.

While the study has yielded valuable insights, it is crucial to recognize its limitations, including its single-center design, the cross-sectional nature of the investigation, potential selection bias, reliance on self-reported headache data, and limited neurological parameters. Future research avenues may involve exploring biomarkers associated with neuroinflammation or vascular dysfunction in SLE patients with headaches, conducting longitudinal studies to evaluate the impact of various SLE treatment modalities on headache prevalence and severity, investigating genetic factors contributing to the co-occurrence of SLE and headaches, and designing interventions to assess the efficacy of headache management strategies in SLE patients.

Conclusion

Our study underscores the complex relationship between Systemic Lupus Erythematosus (SLE) and headaches, revealing that headaches are a common but multifaceted symptom in SLE patients, with tension-type headaches and migraines being the most prevalent. We observed a significant association between headaches and higher SLE disease activity, particularly in patients with antiphospholipid antibodies, which may serve as an indicator for increased vigilance in managing these patients. Notably, no cases met the criteria for “lupus headache,” challenging the clinical relevance of this classification.

The findings emphasize the need for more precise diagnostic criteria and standardized approaches to managing headaches in SLE. Future research should explore the underlying mechanisms linking headaches to SLE, particularly the role of immune dysregulation, and further investigate the clinical significance of MRI abnormalities in this patient population. Longitudinal studies are also necessary to better understand the progression of headaches in SLE and to identify potential biomarkers for early intervention and tailored treatment strategies.