Spondyloarthritis in Latin America: a difficult-to-diagnose challenge

Abstract

Spondyloarthritis (SpA) presents unique diagnostic challenges in Latin America (LATAM) due to genetic, clinical, healthcare, and sociocultural factors. The Assessment of SpondyloArthritis international Society (ASAS) classification criteria—developed mainly in North America and European populations—may not accurately reflect the LATAM phenotypic variability. Key issues complicating diagnosis include lower human leukocyte antigen B27 (HLA-B27) prevalence, clinical heterogeneity, and inconsistent symptom presentation. Many patients develop symptoms later in life compared to their European counterparts. Extra-articular manifestations like uveitis, enthesitis, and tarsitis are common and may precede the diagnosis, contributing to delays. In addition, inflammatory back pain, often used as a referral criterion, has limited specificity and may lead to misdiagnosis. Healthcare systems in LATAM are often under-equipped to recognize and manage SpA efficiently. General practitioners (GPs) and even non-rheumatologist specialists may lack awareness of hallmark symptoms, leading to prolonged referral processes and multiple misdiagnoses. The average diagnostic delay is around 4.2 years, with women facing even longer delays. Use of classification criteria as diagnostic tools further complicates timely recognition. The ASAS criteria often exclude HLA-B27-negative patients and those without clear imaging findings in sacroiliac joints. This leads to underrepresentation in clinical studies and underestimation of disease burden. To improve diagnosis, a comprehensive clinical evaluation—including history, physical exam, imaging, and laboratory test—by rheumatologists familiar with the local disease spectrum. Tools like magnetic resonance imaging, enthesitis indices (e.g., Mander Enthesis Index, Defining Enthesitis on Ultrasound in Spondyloarthritis Enthesitis Index), and spinal mobility measures (e.g., Bath Ankylosing Spondylitis Metrology Index) should be integrated into clinical practice. There is also a need to validate diagnostic and classification criteria specifically for LATAM populations, incorporating region-specific genetic and clinical profiles. Greater awareness, earlier specialist referral, and locally tailored criteria are essential to reduce diagnostic delays and improve outcomes for patients with SpA in LATAM.

Clinical challenge

Spondyloarthritis (SpA) is frequently underdiagnosed in Latin America (LATAM), partly due to challenges in the application of existing classification criteria. In addition, these criteria may not fully capture the clinical and epidemiological characteristics of SpA within the region, as some do not meet the established definitions, which can limit the representation of Latin American patients in clinical trials and epidemiological studies. This situation is further influenced by limited public awareness, suboptimal referral pathways to specialized care, and the absence of a universally accepted diagnostic gold standard.^1–3

The objectives of this narrative review were to highlight the problem of SpA diagnosis in LATAM and to present a proposal for a better diagnostic approach to the disease.

Background

SpA comprises a heterogeneous group of immune-mediated inflammatory diseases that, despite their variability, share characteristic clinical, laboratory, and imaging features. Historically, classification of SpA has been based on clinical manifestations and radiographic findings, with ankylosing spondylitis (AS) regarded as the prototype. The spectrum also includes psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease-associated SpA (IBD-SpA), acute anterior uveitis (AAU), and undifferentiated SpA (uSpA).^1–4

The diagnosis of SpA relies on identifying characteristic patterns of symptoms, clinical signs, and diagnostic test results in individual patients, guided by clinical expertise and the exclusion of mimicking conditions. In the early stages, many rheumatic diseases present with non-specific manifestations and often lack pathognomonic features. Therefore, diagnostic criteria must be sufficiently broad to account for disease variability while still enabling the accurate identification of affected individuals. Rheumatologists play a central role in this process: they must first distinguish rheumatic from non-rheumatic conditions and then differentiate among rheumatic diseases with overlapping clinical features, thereby refining categorization and ensuring accurate diagnosis. ⁵

Currently, SpA is classified according to the Assessment of SpondyloArthritis International Society (ASAS) criteria into axial SpA (axSpA), characterized by predominant axial involvement, and peripheral SpA (pSpA), and defined by predominant peripheral manifestations. For descriptive and research purposes, axSpA is further subdivided into radiographic axSpA (r-axSpA), when sacroiliitis is demonstrated on conventional pelvic radiographs according to the modified New York (mNY) criteria, and non-radiographic axSpA (nr-axSpA), when these radiographic criteria are not met.^6–8

This classification system incorporated magnetic resonance imaging (MRI) of the sacroiliac joints (SI-MRI), allowing the identification of non-ankylotic disease that was not captured by the mNY criteria. Although SI-MRI has shown a specificity (Sp) 95%, its sensitivity (Sn) 53%, and a negative likelihood ratio (LR−) of 0.5 have been relatively modest in some cohorts when compared with the clinical diagnosis established by rheumatologists.^9–12

Classification criteria are designed to define homogeneous groups of patients for therapeutic and epidemiological research and are therefore applied to individuals who have already received a diagnosis. Their development typically relies on expert opinion, which functions as the gold standard and provides the reference against which accuracy is evaluated. It is essential to emphasize that classification criteria are not diagnostic tools and do not account for differential diagnoses. Instead, diagnostic and classification criteria should be viewed as points along a continuum, with the distance between them shaped by factors such as disease prevalence and the clinical characteristics of patients in specific geographic contexts. ¹³ The gap between diagnosis and classification of SpA could have substantial implications in LATAM.

Why might SpA be difficult to diagnose in the LATAM population?

The first problem is genetic diversity. The frequency of human leukocyte antigen B27 (HLA-B*27) in LATAM populations is thought to reflect ancient migratory flows from Asia to the Americas during the Neolithic and Paleolithic periods, as well as subsequent European and African migrations during the colonial era. Environmental factors may also play a role; for example, the selective pressure of malaria, which has been inversely associated with HLA-B27 in several LATAM countries. As a result, the prevalence of HLA-B27 among Latin American patients with SpA is typically below 50%. Other alleles, such as HLA-B15, are also frequent in the region and have been associated with peripheral manifestations of the disease. Taken together, these alleles may occur as often as, or even more often than, HLA-B27 in patients with pSpA in Latin America (LATAM).^14–20

The second problem is clinical heterogeneity. SpA is characterized by cyclic disease activity, with alternating periods of remission and acute relapses. ²¹ This variability in clinical presentation implies that the same patient may exhibit different manifestations at different evaluations. ²² Therefore, all clinical features across time should be considered to ensure an accurate diagnostic approach, rather than waiting for classic symptoms—such as chronic back pain or inflammatory back pain (IBP)—to emerge before pursuing diagnosis.

In LATAM, 75% of patients with SpA develop symptoms before the age of 40, 89% before the age of 45, and 92% before the age of 50. By contrast, in Europe and North America, symptom onset occurs earlier, with 85%, 92%, and 97% of patients developing symptoms before the ages of 40, 45, and 50, respectively. These findings suggest that the age of symptom onset in this region is generally higher than that reported in other SpA cohorts. Moreover, women in LATAM tend to experience symptom onset at an older age than men, highlighting a significant sex-related effect on the age at onset of axial symptoms.^23,24

A positive family history of spondyloarthritis (SpA) is an important feature, reported in 29% of patients in LATAM. Among patients with axSpA in LATAM, the frequency of a positive family history of SpA among patients with axSpA is 23% in those who are HLA-B27 positive and 8% in those who are HLA-B27 negative. In comparison, in Europe and North America, the frequency is higher, at 30% in HLA-B27-positive patients and 16% in HLA-B27-negative patients.^24–26

IBP is a key symptom of axSpA and is often used as a referral parameter from primary care physicians to rheumatologists. However, approximately 13% of patients with IBP receive an alternative diagnosis, such as degenerative disc disease, fibromyalgia (FM), mechanical back pain, or systemic lupus erythematosus. The cumulative probabilities of IBP resolution at 5, 10, and 15 years are 19%, 43%, and 49%, respectively. Notably, within the first year of inclusion, the probability of evolving to SpA was 24%. ²⁷

IBP demonstrates good Sn for the diagnosis of axSpA but has limited Sp, negative predictive value, positive predictive value, positive likelihood ratio (LR+), and LR−. Consequently, its diagnostic value in SpA remains limited.^28,29 In a Mexican community, the prevalence of IBP according to the Berlin criteria was 1.3%, and approximately half of these patients fulfilled the ESSG criteria for SpA (0.6%). ³⁰

Interestingly, the global clinical judgment of IBP by rheumatologists—independent of formal IBP criteria—shows greater diagnostic accuracy, which improves further when additional clinical information is considered. Among the individual IBP parameters, “improvement with exercise” has the highest Se, whereas “alternating buttock pain” demonstrates the highest Sp. ²⁸

Uveitis is one of the most frequent extra-articular manifestations of SpA. In LATAM, SpA is the third leading cause of uveitis and ranks between the first and third causes of anterior uveitis.^31–34 It may develop before, concurrently with, or after the diagnosis of SpA. Among patients with SpA-associated uveitis, it represents the first manifestation in 31.8% of cases and coincides with the diagnosis in 15.8%. Uveitis is also strongly associated with HLA-B27, being reported in approximately 50% of cases. Moreover, nearly 40% of patients presenting with uveitis have undiagnosed SpA, with ocular involvement often preceding the rheumatologic diagnosis by up to 5 years and contributing to an average diagnostic delay of approximately 1 year more than SpA patients without uveitis.^35–40

Mid-foot arthritis, also known as tarsitis, is a prominent feature in young patients with SpA and appears to occur more frequently in LATAM than in Europe. Clinically, it presents with pain and swelling in the mid-foot. Radiographic findings range from osteopenia to bone ankylosis, while MRI typically demonstrates bone marrow edema, synovial sheath and bursae swelling, and abundant synovial fluid within the joint space. This manifestation can contribute substantially to disability in patients with SpA.^41–43

Enthesitis is frequently found in the physical examination of SpA patients, but its prevalence could vary according to evaluated sites and the enthesis index used. While there are over 100 enthesis sites, most of which are extra-articular, clinical practice does not fully evaluate them. Consequently, various enthesis indices have been developed for the systematic assessment of some of these sites. The Mander Enthesis Index (MEI) identified 98.5% of SpA patients with at least one enthesitis. The spinal region is the most frequent site of enthesitis, followed by the pelvic region. However, MEI does not evaluate the quadricep insertion into the superior border of the patella, and patellar tendon insertion into the tibial tubercle (they are evaluated in the SPARCC index). In addition, the enthesis of the pubis is not included in many enthesis indices, but it is still an important area that should be evaluated.^44,45

However, clinical examination of enthesis has a relatively low Sn (approximately 20%) compared with imaging modalities. Nevertheless, because it is simple to perform in clinical practice, clinical examination is recommended as an initial approach for the identification of enthesitis, while not providing definitive confirmation of its presence. ⁴⁶ When clinical enthesis is used, the frequency of enthesitis in FM is higher than in psoriasis (PsO) or Psoriatic Arthritis (APs). However, when ultrasound (US) is applied, enthesitis is observed more frequently in APs than PsO and FM. ⁴⁷ In addition, it provides the greatest discriminatory value for distinguishing enthesitis related to SpA from non-SpA conditions, particularly when power Doppler is employed, and the insertion of the Achilles tendon is assessed. ⁴⁸

Recently, the use of the Defining Enthesitis on Ultrasound in Spondyloarthritis (DEUS) Enthesitis Index (DEI), which combines US with clinical examination, has been proposed to provide a more comprehensive assessment of enthesitis. The DEI has better correlation with the C-reactive protein (CRP) than physical examination only. ⁴⁹

The third problem is healthcare systems: Access to rheumatologist care in LATAM varies significantly across countries. In Argentina, patients who believe their symptoms may be related to a rheumatologic disease can directly access rheumatologist care. In Colombia, however, patients must first see GPs for an initial assessment. These practitioners may then refer them to a non-rheumatology specialist, who subsequently refers them to a rheumatologist. In addition, access to rheumatologists in LATAM is influenced by the type of health insurance system in place. In Mexico, the private health system allows for direct access to rheumatologists. By contrast, patients within the public health system must first be evaluated by GPs or non-rheumatology specialists before being referred to a rheumatologist. A common issue affecting access to rheumatologists in LATAM is the significant variability in the rheumatology workforce across different countries. For example, the ratio of rheumatologists to the population varies widely, with Uruguay having the highest rate at 1 rheumatologist per 27,426 inhabitants, while Nicaragua has the lowest at 1 rheumatologist per 640,648 inhabitants. ⁵⁰ This disparity could lead to delays in the diagnosis of diseases.

The diagnostic journey for patients with axSpA is often long and challenging. In LATAM, the average delay in diagnosis is 4.2 years, although in some cases, it may be even longer.^23,51,52 Females experience significantly longer diagnostic delays than males, largely due to the lower frequency of typical IBP and the higher prevalence of upper thoracic, cervical, or widespread pain. Furthermore, radiographic progression in females is often less severe and slower, which further complicates timely recognition and diagnosis. ⁵³

Some GPs are not familiar with the terms mechanical BP and IBP and often lack confidence in assessing patients with these symptoms. Among those who are aware of IBP, only a few can recall a limited number of its characteristic features. Overall, GP knowledge of other clinical manifestations of axSpA is limited, with particularly low awareness of enthesitis, alternating buttock pain, and dactylitis.^54–56 Similar challenges are also observed among specialists: fewer than one-third of consultants can identify all eight described features, although the majority can recognize at least four. ⁵⁷

Patients felt they had been overly deferential in consultation and had not sought recognition that they may have something more serious than was being implied. ⁵⁸ Approximately 96% of patients with SpA receive at least one misdiagnosis before the correct diagnosis is established, and consultations with non-rheumatologists are associated with longer diagnostic delays. ⁵⁹ Patients’ tendency to ignore symptoms was partially influenced by previous unsatisfactory experiences with healthcare professionals (HCPs). ⁵⁸

The configuration of healthcare services and the duration of consultations were perceived as suboptimal, with referral to a rheumatologist often considered a major cause of delay. The referral process was described as slow and complex, with poorly defined steps and outcomes, frequently leading to patients being assessed by multiple specialties with little coordination or rationalization. ⁵⁸

HCPs perceive axSpA as difficult to diagnose, as one of the main contributors to delayed diagnosis. Other factors cited include limited public and professional awareness, suboptimal healthcare practices, patient-related behaviors and characteristics, and challenges in patient–HCP interactions. ⁵⁸

Access to advanced imaging in LATAM differs significantly from country to country and even within the same country. In small- or medium-sized cities, obtaining these imaging services can be challenging, often requiring referrals to larger cities. In high-complexity hospitals, access to MRI is generally more straightforward. By contrast, in medium- or low-complexity hospitals, patients frequently need to be referred to facilities that offer MRI services, which can result in waiting times of weeks or even months for their scheduled exam.

The fourth problem is the use of classification criteria as diagnostic criteria. A key factor contributing to the gap between diagnosis and classification in LATAM is that the ASAS classification criteria were primarily developed in European and Asian populations, which represented 59% and 35% of the original sample, respectively. Canada contributed 3% of the sample. In addition, the considerable heterogeneity observed among SpA cohorts across different regions—such as variations in the frequency of HLA alleles, arthritis, and enthesitis—limits the external validity of these criteria when applied to Latin American patients.^7,60–62

The peripheral classification of ASAS includes the presence of sacroiliitis on imaging. However, radiographic sacroiliitis (SI-Rx) is a defining feature of r-axSpA; its inclusion as a criterion for pSpA can lead to the misclassification of axSpA patients as pSpA, simply because they did not fulfill the axSpA criteria at the time of evaluation or because the predominant symptom is not axial pain. These patients are, in fact, axial, but due to factors such as fluctuations in symptoms between periods of remission and high disease activity, the modification of clinical manifestations with nonsteroidal anti-inflammatory drugs (NSAIDs), and the reduction of pain following complete ankylosis.^63–65

Rheumatologists can diagnose approximately 80% of patients who have definitive SpA 2 years after the initial evaluation, using comprehensive diagnostic tools such as patient history, physical examination, laboratory tests, and imaging, and a 2-year follow-up will allow the diagnosis of the remaining 20% of patients with definitive SpA. A 2-year follow-up will allow the diagnosis of the remaining 20% of patients with definitive SpA. ⁶⁶

This is particularly evident in European cohorts; however, in LATAM, the proportion of patients receiving a definitive diagnosis at the first assessment, even with a complete diagnostic work-up, may be lower, and longer follow-up may be required to establish an accurate diagnosis. Nevertheless, no studies were identified that confirm or refute this hypothesis.

The fifth problem is sociocultural and awareness factors. Many patients reported that the nature of their initial symptoms contributed to delays in the diagnosis of axSpA. They suspected that when early manifestations did not predominantly involve the lower back or pelvis, suspicion of axSpA was often not raised until later in the course of the disease. Patients’ tendency to ignore symptoms was partly influenced by prior unsatisfactory consultations with healthcare practitioners (HCP). ⁵⁸

In some European countries, the prevalence of SpA—when the entire spectrum is considered, not only r-axSpA—even exceeds that of rheumatoid arthritis (RA). ⁶⁷ In LATAM, the prevalence of SpA is 0.52%, although this figure varies by country, influenced by differences in methodology and the specific characteristics of each population. Notably, the prevalence tends to decrease progressively toward the south of the region.^68–72

In LATAM, epidemiological descriptions of SpA have focused predominantly on r-axSpA; this approach may overlook a substantial proportion of patients with nr-axSpA and pSpA, for whom epidemiological data are far more limited.^73–77 The prevalence of pSpA may be comparable to, or even greater than, that of axSpA, because theirs could be misclassified as having seronegative RA or FM, other musculoskeletal disease, or remain undiagnosed. As a result, they are often excluded from epidemiological studies and underrepresented in regional data.

In one LATAM cohort, the pSpA was the predominant subtype of SpA, and this trend may be similar in other cohorts across the region. This group of patients was classified as uSpA and may represent up to 48% of patients in Mexico and 39% in Colombia. In these patients, spinal pain episodes are characterized by a combination of mechanical and inflammatory features, and they also present with a lower frequency of HLA-B*27, which makes their diagnosis and classification more difficult using the ASAS criteria.^17,20,64,78

What could be done in LATAM to improve the diagnosis of SpA?

Latin American patients who are suspected of having SpA—characterized by chronic back pain (more than 3 months), alternating gluteal pain, arthritis with negative or low-titer rheumatoid factor, and negative antibodies against citrullinated proteins without erosions, as well as signs like enthesitis, dactylitis, AAU, psoriasis, or inflammatory bowel disease—should be evaluated by an expert rheumatologist. The rheumatologist will conduct a detailed medical history, perform a complete physical examination, and order laboratory tests, including CRP, erythrocyte sedimentation rate, and HLA class I. X-ray images of the cervical and lumbar spine, pelvis, hands, ankles, and feet will also be conducted. Once a diagnosis is made, the rheumatologist can classify the disease according to the standard criteria (Figure 1). None of the many SpA features suffices to make a definitive diagnosis of SpA. The sum of positive and negative findings and ruling out other diseases that may simulate SpA are required to diagnose the disease. ⁶⁶

Figure 1.

Approach to a patient with suspected spondyloarthritis.

Sex and age should not be used as criteria to exclude or include patients with suspected SpA. Both females and males can develop the disease, and they may experience similar frequencies of certain subtypes of SpA. Therefore, both sexes should be evaluated equally during the diagnostic process for SpA.^24,53,79

It is important to ask whether the patient has back pain because this is a very common symptom that the patient himself can overlook. They may associate it with other conditions, such as work activities, trauma, or bad posture, and it may not be the main symptom that motivated the patient to consult. Therefore, an adequate and complete evaluation of this symptom is necessary to guide differential diagnoses.

Into the back pain anamnesis are as follows: the time of evolution (acute if back pain is less than 4 weeks, subacute if back pain is between 4 and 12 weeks, and chronic if back pain is more than 12 weeks), localization of back pain (cervical, thoracic, lumbar, sacrum), back pain severity (visual analog scale), pain characteristics (stabbing, electrical, burning, freezing, pressure, weight-type pain), back pain schedule (morning, evening, intermittent, constant), irradiation, pain aggravating, or mitigating factors (relationship with walking and resting, changes with position, exercise or rest). ⁸⁰

The positive family history of SpA in Latin American patients with suspected SpA is linked to the presence of HLA-B27 and axSpA. However, this association is only observed in 27% of SpA patients. Consequently, the absence of a family history should not be used to rule out the disease, particularly in regions where the prevalence of HLA-B27 and axSpA is low, and where other subtypes of SpA are more common. ²⁶

Enthesitis is an important indicator in SpA, making its thorough and systematic evaluation essential. MEI is one of the best tools for assessing enthesitis in both axSpA and pSpA. Along with the MEI, the evaluation should include the quadricep insertion at the superior border of the patella, the patellar tendon insertion at the tibial tubercle, and the enthesis of the pubis, and the use of US. ⁴⁴

There are many tests to evaluate the sacroiliac joint (SIJ) pain on physical examination (FABER/Patrick test, Thigh Thrust Test, Gaenslen Test, Gaenslen Test Modified Technique, Compression Test, Distraction Test, Yeoman Test, Gillet test, Sacral thrust, SIJ pain), each with a different diagnostic performance and reproducibility in the studies. The Gaenslen test and the thigh thrust are the most reliable, and the latter has good sensitivity with acceptable Sp. Combining several positive sacroiliac stress tests (at least three tests) could improve the diagnostic yield for sacroiliac pain, but alone, they do not allow precise differentiation of the etiology.^81–84

The evaluation of SIJ pain on physical examination should include at least three sacroiliac stress tests, and one of these is the Thigh Thrust Test because it has good reproducibility and Sp. ⁸⁵ Measuring spinal mobility could be assessed according to the Bath Ankylosing Spondylitis Metrology Index (BASMI) to standardize the measurement of spinal mobility. ⁸⁶

Spinal mobility is important because it is associated with physical function, and it is an independent predictor of treatment response or quality of life, but optional domains into the core domain set for axSpA. The BASMI has moderate or excellent agreement with global structural damage (BASRI, mSASSS), and it was superior to individual mobility measures.^86–88 This clinimetric tool may require validation in the Latin American population.

CRP has low sensitivity but high specificity and should be conducted in all patients suspected of having SpA. In cases where the baseline CRP is normal, it can be repeated within the following 16 weeks.^12,89 The CRP is an inflammatory marker in SpA; it has a positive correlation with male sex and a negative correlation with age. CRP changes with the use of NSAIDs. This test has Sn and Sp of 35% and 85%, respectively. However, one-half of patients with normal CRP levels at baseline could have high CRP levels within the following 16 weeks.^12,89,90

Imaging techniques play a crucial role in diagnosing and classifying SpA, offering complementary benefits. MRI is particularly useful for assessing acute changes in the SIJ that may not be visible on SIJ X-rays. By contrast, X-rays are more effective for evaluating chronic structural changes in these joints. Pelvic radiography is valuable for detecting enthesopathy, a feature that can be identified at early stages but may be overlooked over time.^91–94

All patients with suspected SpA undergo anteroposterior pelvic, along with anteroposterior and lateral lumbar X-rays, and lateral cervical X-ray. On the anteroposterior pelvic X-ray, the one-third lower of the SIJ is evaluated to recognize sacroiliitis, which is classified according to the mNY criteria. In addition, enthesopathy is another characteristic of SpA, and the pelvis is a common place to find it.^92,94 On the anteroposterior and lateral cervical and lumbar X-rays, the presence of syndesmophytes and facet joint ankylosis is another finding in SpA.^95,96

The SIJ-MRI is one of the most useful tools to diagnosis SpA. It has good LR+ [Bone Marrow Edema (BME): 14.7, and structural damage: 10.7], but lower LR−. The new definitions for active and structural MRI lesions in SIJ have determined lesion cutoffs that optimally define an active or structural MRI lesion considered typical of axSpA. This preliminary cutoff (2021) may slightly increase the Sp of the quantitative part of the previous (2009) cutoff for MRI inflammatory lesions.^12,97,98 It could not be necessary to repeat the SIJ-MRI after 3 months or 1 year in patients with suspected SpA, given that baseline negative SIJ-MRI changes to positive in 7% or fewer cases. Two reasons to repeat the SIJ-MRI are male sex and HLA-B*27 positive, because they are independent factor to positive SIJ-MRI in the following. In this case, 27% of suspected SpA patients with baseline negative SIJ-MRI change to positive SIJ-MRI.^99,100

SIJ-MRI can be performed on all patients suspected of having SpA. It is important for a skilled radiologist or rheumatologist to evaluate the results to enhance diagnostic accuracy. While SIJ-MRI is an important tool in the diagnosis of SpA, it should not be used in isolation to either confirm or rule out the condition. For proper interpretation, both the rheumatologist and radiologist should have access to the patient’s complete clinical history and relevant laboratory results, and they should adhere to the current guidelines for reporting SIJ-MRI findings.^101,102

Perspectives

Recently, two disease models based on HLA have been proposed. The first, associated with HLA-B27, is characterized by predominant axial involvement, sacroiliitis, and a cytokine profile suggestive of a Th2 immune response (axial model). The second, linked to HLA-B15, is associated with enthesitis, absence of SI-Rx, and a cytokine profile consistent with an innate immune response (enthesitis model). In addition, a complementary model focused on cytokine patterns has been described, in which specific cytokine profiles are associated with non-HLA-B27 SpA phenotypes. ¹⁰³ These models need to be validated in the LATAM population with SpA.

Understanding and defining a particular disease is crucial to estimating its burden on the population, its inclusion in clinical trials, and implementing an appropriate treatment plan. However, defining a particular disease can be difficult, particularly without a sensitive and specific marker. Hunder said in an editorial about the use and misuse of classification and diagnostic criteria for complex diseases that “We must keep in mind that classification criteria and diagnoses are not diseases. They are descriptors that change as new knowledge is acquired.”^104,105

It is worth noting that advances in knowledge in the field of SpA in the last 50 years have been developed predominantly in countries in the northern hemisphere, taking as a reference population from Europe, the United States, and Canada, where axial forms of the disease are common. In recent years, long-term follow-up of cohorts of Latin American patients has made it possible to visualize a disease model where peripheral symptoms are mixed with mild and alternating degrees of axial skeleton involvement. One of the objectives of this work is to draw the attention of researchers to include these patients in new developments involving these diseases.

However, in the absence of globally or regionally validated diagnostic criteria for SpA, classification criteria are often used to support diagnosis. Although these criteria are widely applied, many rheumatologists believe that the current ASAS criteria for axSpA require updating. Their sensitivity is particularly limited in patients who are HLA-B27-negative, as they cannot be classified through the “clinical arm,” and in those without sacroiliitis, since positive SI-MRI findings are present in only 36% of patients at diagnosis, and SI-Rx is both a late manifestation and difficult to interpret in less severe forms. These limitations hinder patient inclusion in the “imaging arm.”^97,106,107

Until validated diagnostic criteria are established, it is important to recognize that existing classification criteria may have some limitations in accurately diagnosing and classifying the disease. Therefore, these criteria should not replace the judgment of a rheumatologist, but they could accompany the diagnosis process. Any developed classification criteria should be validated specifically in the Latin American context. This adaptation should consider different HLA alleles, include a comprehensive evaluation of enthesitis, incorporate additional imaging findings, and weigh the characteristics of the disease appropriately. These modifications are necessary to reflect the situation of SpA in LATAM, ultimately allowing for greater participation in clinical and epidemiological studies.

Limitations

This narrative review has several limitations. First, the evidence summarized is derived from heterogeneous studies conducted across different Latin American countries, each with variability in healthcare structures, diagnostic capacities, and population characteristics. This heterogeneity may limit the generalizability of some observations to the entire region. Second, although the manuscript discusses diagnostic challenges related to genetic diversity, clinical heterogeneity, healthcare access, and the use of classification criteria, many of the referenced studies were not specifically designed to validate diagnostic approaches for SpA in LATAM. As such, the conclusions drawn should be interpreted with caution.

Third, the review highlights potential differences between Latin American and non-Latin American populations, particularly in relation to HLA-B alleles, age at symptom onset, and extra-articular manifestations; however, comparative data remain limited, and some hypotheses—such as longer time to diagnosis or the predominance of peripheral phenotypes—require confirmation in prospective, regionally representative cohorts. Fourth, although we discuss gaps in imaging performance and referral pathways, the availability and quality of imaging technologies (e.g., MRI) differ substantially across countries and even within the same country, which may influence both diagnostic delay and disease characterization.

Finally, as a narrative review, this article is subject to the inherent limitations of this study design, including potential selection bias in the literature reviewed and the absence of a systematic appraisal of study quality. Despite these limitations, this work synthesizes relevant regional data and expert insights, aiming to promote a more accurate understanding of SpA in LATAM and to encourage the development of diagnostic strategies tailored to the regional context.

Conclusion

SpA in LATAM poses significant diagnostic challenges driven by genetic diversity, clinical heterogeneity, sociocultural factors, and disparities in healthcare access. The lower prevalence of HLA-B27, the frequent presence of peripheral and extra-articular manifestations, and limitations in applying ASAS classification criteria—developed largely outside the region—contribute to delayed diagnosis and underrepresentation of Latin American patients in research. Improving diagnosis will require greater awareness among HCPs, earlier referral to rheumatology, and the use of comprehensive clinical, laboratory, and imaging assessments. Importantly, region-specific validation of diagnostic and classification tools is needed to better reflect the Latin American disease spectrum and ultimately enhance patient outcomes.