The current state of systemic lupus erythematosus care in the Philippines: a narrative review

Systemic lupus erythematosus, or SLE, is a multiorgan autoimmune disease characterized by the production of autoimmune antibodies toward nuclear antigens, immune complex deposition, and chronic inflammation of different organs of the body [ 1 ]. SLE is a relapsing-remitting disease with unpredictable flares in between periods of clinical quiescence of varying duration. The patterns of disease activity can be long quiescent, relapsing-remitting, and persistently active [ 2 ]. SLE remains a public health concern globally, including in the Philippines. However, there are still limited studies on SLE in the Philippines. Hence, this study synthesized the available literature on the epidemiology, diagnosis, and management of SLE in the Philippines. This narrative review paper also identified gaps in clinical management and potential areas for health research in the country. The actual prevalence and incidence of lupus in Asia and the Philippines are unknown, in part due to the lack of other centralized estimation efforts aside from the Community Oriented Program for the Control of Rheumatic Diseases of the World Health Organization (WHO) and the International League of Associations for Rheumatology [ 3 ]. Prevalence approximations vary, ranging from 3 to 70 cases per 100,000 people in Asian countries [ 3 ]. In Malaysia, the estimated prevalence is 43 persons per 100,000, with immigrant Chinese having the highest rates, followed by Indians, then ethnic Malays [ 4 ]. The Asian cohort in Hawaii was also found to have a higher prevalence of SLE compared with Caucasians [ 4 ]. The incidence in Hong Kong in 2006 was 2.8 in the general population and 5.1 in females, whereas the overall incidence in Japan was 0.9 [ 3 ]. In another study, it was described that the prevalence of SLE in South Korea (20 to 26.5 per 100,000 Person-Years [PY]) was lower than that of in China (30 per 100,000 PY) and of Taiwan (67.4 per 100,000 PY), with the prevalence of SLE in North America trumping all East Asian countries at 241 per 100,000 PY, which remains consistent with previous studies [ 5 , 6 ]. There is a paucity of prevalence and incidence data in the Philippines due to a lack of centralized cohorts and representative epidemiologic studies. Despite this, institutional cohorts, registries, and studies provide insights into the burden of lupus in the Philippines. Filipino females are primarily affected by SLE, with female-to-male ratios ranging from 20~30 to 1, and with common ages at diagnosis falling within the second and third decades of life [ 7 , 8 ]. This female preponderance is also seen in juvenile SLE in the country, which has an average age at diagnosis of 14 years old [ 9 - 12 ]. This is consistent with previous reports in South Korea, as analyzed by Han et al. [ 6 ], in which female-to-male ratios were found to range from 6.5:1 to 10:1. About half (52.17%) of all outpatient consults for connective tissue diseases in the Philippines are due to lupus [ 13 ]. Some of the most common initial manifestations of SLE in Filipino adults include mucocutaneous involvement (e.g., alopecia, malar rash, discoid rash, oral ulcers, etc.), seen in 59% to 86.4%, musculoskeletal impairments (e.g., arthritis) in 61.4% to 68%, hematologic derangements (e.g., anemia, thrombocytopenia, etc.) prevalent in 46% to 63.6%, and renal injury in about 47% to 74% [ 7 , 14 , 15 ]. These local findings echo results in SLE patients in Asia, with respective prevalence rates of 52% to 98% for mucocutaneous, 36% to 95% for musculoskeletal, 26% to 83.8% for hematologic, and 18% to 100% for renal involvements [ 14 ]. Similarly, juvenile SLE patients most commonly present with mucocutaneous lesions (88% to 91%), renal injury (45% to 63%), musculoskeletal complaints (41% to 67.8%), and hematologic problems (35% to 61%) [ 9 - 11 ]. Some of the rarer but equally serious clinical states in Filipino children with SLE are seizures seen in 34.5%, myocarditis in 23.8%, acute kidney injury in 12.6%, and blurring of vision in 10.3% [ 11 ]. SLE patients are also at higher risk for cardiovascular diseases such as myocardial infarction (MI), heart failure, and stroke, with hazard ratios ranging from 1.39 to 6.88, with the pretext that these diseases may be defined differently across countries [ 6 ]. SLE is the most common rheumatologic disease prompting admission in the Philippines [ 8 ]. During the entire course of the disease, it may lead to complications in various organs such as the kidneys (e.g., acute kidney injury, nephrotic syndrome, etc.), blood (e.g., hemolytic anemia, thrombocytopenic purpura, etc.), and mucocutaneous surfaces (e.g., oral ulcers, etc.) [ 7 , 9 , 11 , 14 ]. Furthermore, juvenile SLE has a mortality ranging from 10% to 25% [ 11 ]. Common causes of death in the general population aside from active lupus include septic shock and infections and cardiopulmonary complications such as myocarditis and pulmonary hypertension [ 6 , 9 , 11 ]. Several complications and risk factors during disease have also been found to increase the risk of mortality in juvenile SLE patients, including younger age at diagnosis (odds ratio [OR]: 0.89), occurrence of seizures (OR: 9), pleural effusion (OR: 6.25), myocarditis (OR: 5.89), hemolytic anemia (OR: 3.36), leukopenia (OR: 2.48), and lymphopenia (OR: 2.82) [ 11 ]. The etiology of SLE is complex. There were several risk factors associated with this diseases including genetic and immune factors, environmental exposure, socioeconomic factors, and comorbidities ( Figure 1 ). Molecular determinants of SLE prevalence and disease burden in the Philippines primarily affect nucleic acid repair and immune responses. Single nucleotide polymorphisms (SNPs) in the genes MSH5, HLA-G-HLA-H, and DRB1-DQA1 have been identified to be associated with multiple sclerosis (MS) and SLE [ 16 ]. Additionally, the SNP rs9271366, located in the HLA-G-HLA-H region, has been suggested to have a major role in variants on the haplotype of SLE patients in the Philippines, which is concordant with other studies that analyzed Pacific populations [ 16 , 17 ]. SNP rs9271366 is expressed in patients with MS and can suppress immune responses mediated by natural killer cells, suggesting its involvement in autoimmune diseases [ 18 , 19 ]. The Philippine Genome Center has also investigated SNP rs9271366. It has been implicated in SLE patients from East Asia and Malaysia, highlighting the importance of studying this molecular factor and its interactions with other proteins in the SLE disease process in the Philippine population [ 20 , 21 ]. Profiling the autoantibodies in SLE patients and their first-degree relatives in the Philippines also showed differences from unaffected, unrelated controls. Antinuclear antibody (ANA) positivity was significantly higher in SLE patients and their unaffected first-degree relatives [ 22 , 23 ]. Anti–Sjögren’s-syndrome-related antigen A autoantibodies (Ro/SSA) and anti-double stranded DNA (anti-dsDNA) also had higher occurrences in SLE patients and first-degree relatives (4.94% for anti-Ro/SSA and 1.36% for anti-dsDNA) versus healthy, unrelated controls [ 22 , 23 ]. These autoantibodies, even in asymptomatic cohorts, may further be used to prognosticate overt clinical disease. SLE has been diagnosed in Filipinos between the ages of 5 to 71 years, and anecdotally outside this age range, with an average age of detection at 28.5±11.5 years [ 7 ]. The average interval between the clinical presentation of the disease and the diagnosis of SLE was 6.4±10.8 months in the general population [ 14 ]. One clinical risk factor for SLE flares is endometriosis, aggravating or inducing SLE flares due to suppressed cellular immunity and increased autoantibody formation [ 24 ]. Patients with endometriosis were found to have a higher risk of having SLE (OR 1.36, 95% confidence interval [CI] 1.07 to 1.73; p=0.010) [ 25 ]. Atopic diseases are also important clinical risk factors for SLE. For instance, the presence of atopic dermatitis (AD) increases the risk of developing SLE (OR 1.46, 95% CI 1.05 to 2.04; p=0.020), hypothesized to be a result of upregulating cytokine production by Th2 and Th17 cells, with a concurrent downregulation of IL-2 production by Th1 cells [ 26 ]. Similarly, allergic rhinitis (AR), a disease associated with AD, has also been identified as a risk factor for SLE (OR 1.36, 95% CI 1.08 to 1.72, p=0.009) [ 27 ]. Atopy is generally a proinflammatory state with consequent immune dysregulation attributed to Th2 cell upregulation and IgE production increase, predisposing AD and AR to autoimmune diseases such as SLE [ 27 ]. Lastly, the gut microbiome composition has also been implicated in SLE prognostication, treatment response, and disease development. The levels of Bacillales , Coprobacter , Lachnospira , and Actinobacteria were negatively correlated with SLE risk, while Bacilli , Lactobacillales , and Eggerthella were identified as possible risk factors for SLE onset [ 28 ]. These findings present opportunities for further research on novel SLE treatment modalities, such as probiotics. Lifestyle and environmental risk factors for SLE include smoking, air pollution, and silica exposure. Current smokers were found to be at more risk for developing SLE (OR 1.50, 95% CI 1.09 to 2.08) [ 29 ]. Despite the 2012 Sin Tax on cigarettes in the Philippines, the country was still third in Southeast Asia in terms of smoking prevalence in 2016 at 24%, with an inelastic demand for cigarettes [ 30 ]. Particulate matter, ozone, nitrogen dioxide, and other byproducts of air pollution were also found to induce proinflammatory states as well as DNA hypomethylation, leading to the development of autoimmune disease, demonstrable by an increased risk for elevated SLE disease activity, nephritis, decreased serum C3, and anti-dsDNA positivity [ 31 ]. Notably, fine particulate matter (PM 2.5 ) in the Philippines exceeds the global average set by the WHO, especially in urban centers such as Metro Manila [ 32 ]. Exposure to silica and silicates, more specifically respirable silica dust (i.e., crystalline quartz), has been established as a risk factor for SLE and other systemic autoimmune diseases such as scleroderma and rheumatoid arthritis, among others, where higher doses of exposure were found to lead to increased intensity and exposure of SLE flares [ 33 , 34 ]. Inhaling silica dust is more likely in occupations exposed to silica and in residences in urban areas [ 35 ]. High SLE disease activity, organ damage, and mortality were found to be higher in SLE patients from lower and impoverished socioeconomic classes, highlighting disparities in healthcare globally [ 36 ]. Mood disorders are no exception, however depression was seen to be less frequent among Filipinos with SLE despite having lower socioeconomic status compared with their Southern Californian counterparts [ 37 ]. Patients in the low-income category were found to have higher frequencies of the following alleles, HLA-DRB1*03:01 (p-value [pC]=0.002, OR=3.6, and 95% CI=1.65 to 7.98) and HLA-DRB1*04:05 (pC=0.028, OR=12.9, and 95% CI=1.32 to 124.76) while those in the high-income category had increased frequencies of high-risk alleles such as HLADRB1*07:01 (pC=0.03, OR=2.0, and 95% CI=1.11 to 3.76), as well as HLA-DRB1*11:04 (pC=0.0004, OR=5.1, and 95% CI=2.02 to 13.06), with decreased protective alleles such as HLADRB1*14:06 (pC=0.01, OR=0.3, and 95% CI=0.10 to 0.78) and HLA-DRB1*16:02 (pC=0.04, OR=0.2, and 95% CI=0.05 to 0.94) [ 38 ]. HLA-DRB1*04:05 has been identified in higher frequencies in patients of oriental descent and may be implicated among Filipino SLE patients [ 38 ].

The Philippine Health Agenda for 2016 to 2022 highlights the significant financial burden imposed on families by healthcare expenditures, including those related to SLE [ 16 ]. A cost analysis of 100 pediatric SLE patients in the Philippines revealed an average annual direct cost of 162,764.81 PHP (approximately 2,821.75 USD) per patient, primarily attributable to medication costs [ 12 ]. Meanwhile, the minimum wage in the National Capital Region (NCR) in 2024 has been pegged at 610 PHP (10.47 USD) per day [ 54 ], making this annual cost sum up to 73% of the annual income of minimum wage earners in the capital, a situation that is much worse for geographically isolated and disadvantaged areas in the country. Furthermore, studies indicate that SLE patients in the Philippines allocate a substantial portion of their income to healthcare, with up to 82% of annual income and 25% of household budgets dedicated to medical expenses. This percentage for household healthcare expenditures is beyond the World Bank threshold of 10% [ 90 ], indicating that out-of-pocket costs for SLE care in the country may impoverish Filipino households. Nephritis leading to end-stage renal disease requiring dialysis is a significant cost driver, increasing healthcare costs by 3.5 to 7 times for patients undergoing chronic hemodialysis or those post-renal transplantation [ 12 , 16 ]. Aside from direct costs for SLE patients, indirect expenses, structural issues, and socioeconomic disparities in healthcare pose significant barriers to effective individual- and population-based lupus interventions in the Philippines, especially for those outside of NCR. On average, the country has approximately 3.9 doctors per 10,000 population [ 91 ]. Most doctors are concentrated in NCR, with around 10.6 doctors per 10,000, in contrast to provincial regions with only about 2 doctors per 10,000 [ 91 ]. Among these doctors, there is only 1 rheumatologist per one million Filipinos, underscoring the gravity of the country’s human resource shortage for managing lupus [ 92 ]. Similarly, most of the hospital beds in the country are in the island group of Luzon, with 29% in NCR and 36% in the rest of the island group, and only 20% in Mindanao and 15% in Visayas [ 91 ]. Pressing still are the conditions in public facilities such as overcrowding, prolonged waiting, and inefficient documentation, among others, limiting access for impoverished Filipinos with SLE who consequently delay care or forego it altogether [ 44 ]. The COVID-19 pandemic also greatly affected healthcare access among SLE patients. During the pandemic, SLE patients had to use teleconsultations. In a local study, around 62.7% of SLE patients had an average of a year-long interruption in medical care [ 93 ]. Approximately 22.7% discontinued at least one of their drugs for SLE control, which resulted in lupus flares and hospitalizations among SLE patients [ 93 ]. Another local study reported interruptions in the supply of HCQ and methotrexate during the COVID-19 pandemic, which was associated with the presence of muscle pain, rash, and joint pains among SLE patients [ 51 ]. The scarcity of studies, including financial toxicity research, that assess SLE-specific direct expenses such as diagnostics and medications, as well as indirect costs including human resources and infrastructure, significantly preclude comprehensive policymaking and targeted strategies that may alleviate the financial burden on SLE patients and their families. These insights can inform policy decisions to improve affordability, ensuring that all individuals, regardless of socioeconomic status, have equitable access to essential healthcare services for lupus.

This review is a comprehensive account of the SLE situation in the Philippines. The absence of national data registries and the reliance on available institutional records magnify the difficulty in estimating the burden of SLE in the Philippines. Furthermore, local clinical practice guidelines are yet to be published. SLE and its management in the Philippines reflect the overall state of our healthcare system. Costs for SLE diagnosis, treatment, and management generally remain blatantly toxic for most Filipinos, from early detection up until managing complications. This is compounded by the almost entirely out-of-pocket financing system for healthcare in the country. Implementing the Universal Healthcare Act may potentially alleviate this burden should all stakeholders, including the medical community and the national government, undertake a comprehensive approach to lupus care. More research on the diagnosis, treatment, and prognosis of SLE in the Philippines is needed. Once the actual burden of the disease has been described and targeted, population-based interventions will be possible. We also acknowledge the structural barriers to comprehensive lupus care due to social determinants in the country and call on stakeholders to provide safe, equitable, and effective measures to control the burden of lupus in the Philippines.