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 Table of Contents  
Year : 2022  |  Volume : 24  |  Issue : 1  |  Page : 71-75

Pure peripheral spondyloarthritis, is it exceedingly rare? A real-world experience from an Indian tertiary care hospital

1 Department of Rheumatology, Command Hospital Southern Command, Pune, Maharashtra, India
2 Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Geriatrics, Armed Forces Medical College, Pune, Maharashtra, India
4 Centre for Chronic Conditions and Injuries, Public Health Foundation of India (PHFI), Gurugram, Haryana, India
5 Department of Radiology, Command Hospital Southern Command, Pune, Maharashtra, India

Date of Submission20-Aug-2020
Date of Decision27-Aug-2020
Date of Acceptance26-Nov-2020
Date of Web Publication01-Apr-2021

Correspondence Address:
Col Arun Hegde
Department of Rheumatology, Command Hospital Southern Command, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_117_20

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Background: Peripheral spondyloarthritis (pSpA) is usually associated with psoriasis, inflammatory bowel disease, or preceding infection (called reactive arthritis). Pure pSpA is a clinical entity wherein there are enthesitis, dactylitis, or arthritis, without any of the above-associated conditions. We aimed to describe the clinical, laboratory, radiological, and management profile of pure pSpA, among patients with pSpA presenting to the rheumatology outpatient department. Materials and Methods: In this retrospective, observational study, medical records of all the patients diagnosed as pSpA by a rheumatologist, between January 1, 2016, and December 31, 2018, were included. Among these, thirty patients qualified to be called pure pSpA, and we reported their demographic characteristics (age and sex), clinical features (onset of disease, clinical signs, and symptoms), laboratory parameters (erythrocyte sedimentation rate, hemoglobin, and C-reactive protein), radiological findings, and treatment pattern. Results: Thirty patients fulfilled the criteria for pure pSpA. The mean age (standard deviation) of the patients at onset was 32 ± 5.8 years. The mean disease duration before diagnosis was 9.7 months. Arthritis, enthesitis, and dactylitis were present in 29 (96.7%), 8 (26.7%), and 9 (30%) patients, respectively. Eighteen (60%) patients had monoarthritis, while 11/30 (36.7%) had oligoarthritis, at presentation. HLA B27 was positive in 24/30 (80%) patients. Seven patients (23.3%) had bilateral sacroiliitis on imaging and two (6.7%) had unilateral sacroiliitis. Twenty patients (66.7%) required conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while two (6.7%) required biological DMARDs in the form of anti-tumor necrosis factor-alpha inhibitors. Conclusion: Pure pSpA is a relatively rare clinical disease which presents with either a mono or oligoarthritis and shows good treatment response to csDMARDs.

Keywords: Dactylitis, enthesitis, peripheral spondyloarthritis, pure peripheral spondyloarthritis, undifferentiated spondyloarthritis

How to cite this article:
Hegde A, Mangal V, Vasdev V, Singh K, Bhanu KU. Pure peripheral spondyloarthritis, is it exceedingly rare? A real-world experience from an Indian tertiary care hospital. J Mar Med Soc 2022;24:71-5

How to cite this URL:
Hegde A, Mangal V, Vasdev V, Singh K, Bhanu KU. Pure peripheral spondyloarthritis, is it exceedingly rare? A real-world experience from an Indian tertiary care hospital. J Mar Med Soc [serial online] 2022 [cited 2023 Apr 1];24:71-5. Available from: https://www.marinemedicalsociety.in/text.asp?2022/24/1/71/312884

  Introduction Top

Spondyloarthritis (SpA) is a distinct group of inflammatory arthritis that can involve axial skeleton or appendicular skeleton or both. Depending on the predominant clinical feature, SpA can be further classified as axial SpA (axSpA), primarily affecting the axial skeleton, that is, the spine and the sacroiliac joints (SIJs), and peripheral SpA (pSpA), which predominantly presents as arthritis, enthesitis, and/or dactylitis. The worldwide prevalence of axSpA ranges between 0.20% and 1.61%,[1] while its prevalence in India is around 0.03%.[2] Data are lacking on the exact prevalence of pSpA, however the few cohorts that are available show similar results, with the Dutch SpA cohort,[3] Spanish Esperanza cohort,[4] and the Belgian Be-Giant cohort[5] observing prevalence rates of 26.8%, 22.8%, and 28.5% of the axSpA population, respectively. Compared with axSpA, patients with pSpA are diagnosed faster due to clinical signs of inflammation (i.e., arthritis or dactylitis) and tend to be older at disease onset. Patients with pSpA also have an equal sex distribution.[3]

Previously, pSpA and the entire spectrum of SpA were classified as per European Spondyloarthropathy Study Group (ESSG) and Amor criteria.[6],[7] These criteria were generated in the 1990s and had many limitations. Currently, the Assessment of Spondyloarthritis International Society (ASAS) classification criteria, developed in 2011, is used for the classification of pSpA[8] [Table 1]. The ASAS criteria has a higher sensitivity (77.8%), as compared to the ESSG (62.5%) and the Amor criteria (39.8%), with reasonable specificity (82.9%).
Table 1: The assessment of spondyloarthritis International Society classification criteria for peripheral spondyloarthritis

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Peripheral SpA is usually associated with psoriasis, inflammatory bowel disease (IBD), or preceding infection (called reactive arthritis). Still, some patients cannot be classified into any of the above, and this entity is labeled as undifferentiated pSpA.[6],[7],[9],[10] The nomenclature of undifferentiated pSpA has subsequently changed, and now it is often referred to as pure pSpA[11] or pSpA without an associated illness. There is a paucity of data on pure pSpA from our country.

  Materials and Methods Top

This was a retrospective, observational, hospital record-based study carried out in a tertiary care hospital in India. The study population comprised 100 patients, diagnosed as pSpA, by a rheumatologist, in the outpatient department, as obtained from the medical records.

The study aimed to describe the clinical characteristics of pure pSpA. The objective of the study was to describe the clinical, laboratory, radiological, and management profile of pure pSpA, among patients with pSpA presenting to the rheumatology outpatient department (OPD) of a tertiary care hospital.

Patients aged >16 years who met the ASAS classification criteria for pSpA were included in this study[8] [Table 1]. Patients with significant axial involvement (defined by the predominant symptom of inflammatory low backache with significant early morning stiffness, or alternating buttock pain at presentation) were excluded from the study. Similarly, patients with associated diseases such as psoriasis, IBD, reactive arthritis, and other known causes of inflammatory arthritis were also excluded from the study. The study period was from January 1, 2016, to December 31, 2018.

The prevalence of axSpA in India is 0.03% axSpA population, and the prevalence of pure pSpa is 6.5% out of this 0.03%. This suggests that the pure pSpa is a rare disease with a prevalence of 1.9/100,000 population. Taking the precision to be 5% and 95% level of confidence, the sample size required is 1. However, we analyzed the hospital records of thirty patients of pure pSpA.

Patients' hospital medical records were analyzed in detail by a team comprising of an internist and two rheumatologists for the demographic profile including age at onset; time to diagnosis; gender; number of joints involved; pattern of arthritis, enthesitis, and dactylitis. All patients had undergone screening for uveitis, by an ophthalmologist.

Laboratory investigations such as complete hemogram, liver function tests, renal function tests, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and HLA B27 were analyzed. Hematological parameters were measured using Siemens advia 2120i autoanalyzer (Erlangen, Germany), and biochemical parameters were measured using Siemens Dimension RxL Max (Erlangen, Germany). ESR was measured using the Westergren method. CRP was estimated using nephelometry and HLA B27 was done by polymerase chain reaction BAG Diagnostics GmbH (Lich, Hessen, Germany). All the patients had undergone SIJ imaging in the form of a short-axis posterior-anterior view (SAPA) radiograph.

We reported summary statistics for the continuous measures (age and ESR) as mean (standard deviation [SD]) and categorical variables (sex, clinical signs and symptoms, and treatment profile) as n (%). The data were collected and compiled in Microsoft Excel version 2019 and analyzed using Stata Statistical Software, Release 13: Stata Corp. 2013, StataCorp LP, College Station, TX, USA.

The institutional ethics committee approved this study, vide IEC S. No: IEC/2020/228.

  Results Top

Out of a total of 100 patients diagnosed as pSpA in the rheumatology OPD from January 1, 2016, to December 31, 2018, 30 patients were classified as pure pSpA. The mean age (SD) of the patients at disease onset was 32 ± 5.8 years. Twenty-six patients (86.6%) were below 40 years of age, and only four (13.4%) were ≥40 years of age. All the patients were male. The average disease duration prior to diagnosis was 9.7 months (range: 1 month – 5 years).

Twenty-nine (96.7%) patients had arthritis at presentation. The knee, ankle, and wrist joints were involved in 27 (90%), 12 (41%), and three (10%) patients, respectively. None of the patients had a shoulder, hip, or small joint arthritis. Temporomandibular joint involvement was not recorded in any of the patients. Two patients (6.7%) had involvement of all the three joints. Eighteen patients (60%) had monoarthritis, whereas 11 (36.6%) had oligoarthritis, at presentation. One patient did not have arthritis, but presented with enthesitis and HLA B-27 positivity, as a presenting feature. [Figure 1] depicts the pattern of joint involvement. All the patients had asymmetrical pattern of joint involvement. Eight (26.7%) patients had dactylitis at presentation. Seven (23.3%) had dactylitis of great toe, whereas one (3.3%) had the right middle finger dactylitis. Nine patients (30%) had enthesitis. Six patients had heel enthesitis, whereas three patients had enthesitis at posterior superior iliac spine. [Figure 2] depicts the various musculoskeletal manifestations. Six patients (20%) had past history of inflammatory back pain (IBP). None of the patient had eye involvement in our study.
Figure 1: Pattern of joint involvement. Numbers indicate absolute number of patients

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Figure 2: Details of musculoskeletal manifestations. Numbers indicate absolute number of patients

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The mean ESR was 33.6 ± 26.3 mm. The mean C-reactive protein levels were 200 ± 284.76 mg/L. Twenty-four patients (80%) were HLA B-27 positive.

Seven patients (23.3%) had bilateral sacroiliitis on imaging, and two (6.7%) had unilateral sacroiliitis. Among these, two were HLA-B27 negative. All patients received nonsteroidal anti-inflammatory drugs (NSAIDs). Twenty (66.7%) patients also required conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in the form of sulphasalazine (SSZ). Two (6.7%) patients required biological disease-modifying anti-rheumatic drugs (bDMARDs) because of high disease activity, despite three months of csDMARD intake, after ruling out latent tuberculosis by means of a QuantiFERON TB Gold test and chest radiograph. One patient received etanercept 0.6 mg/kg SC (4 doses), while the other received infliximab, 5 mg/kg (2 doses).

  Discussion Top

Peripheral SpA by itself is not such a common diagnosis, as discussed earlier. There are limited studies on the pure form of pSpA, with Malaviya et al.,[11] observing that it constituted 6.2% of their cohort of 405 axSpA patients. This pure form of pSpA was probably first described by Prakash et al. in 1983,[12] in their study conducted at AIIMS, New Delhi. In our study, pure pSpA constituted 30% of pSpA, The age at onset of disease in our study cohort (32.06 years) was higher than that of other studies by Prakash et al.[12] (21.4 years) and Malaviya et al.[11] (23.2 years), but similar to the patients of van der Linden cohort[9] (32.2 years). All patients in our study were male, compared to that of other studies, that is, 88% (Prakash et al.[12]), 72% (Malaviya et al.[11]), and 63.1% (van der Linden et al.[9]).

Arthritis is the most common symptom in pSpA across the limited studies available, with a prevalence ranging between 96% and 98%.[5],[13] Arthritis in pSpA predominantly involves lower limb joints, especially knee and ankle.[6],[8] Rarely, small joints in upper limbs, shoulder, hip, sternoclavicular, pubic symphysis, and temporomandibular joints can be involved. Our study had knee, ankle, and wrist joint involvement in 90%, 41%, and 10% patients, respectively, which was in consonance with Indian studies. Malaviya et al.[11] and Prakash et al.,[12] in their studies on Indian population, reported monoarthritis in 0% and 8%, oligoarthritis in 72% and 52%, and polyarthritis in 28% and 40% of the patients, respectively. Contrastingly, in our study, the predominant presentation was that of monoarthritis (60%), followed by oligoarthritis (36.6%). This could be due to the heterogenic nature of the Indian population, with varying ethnicities.

Enthesitis has a prevalence of 41%–48% across various studies on pSpA.[5],[13] The most commonly affected sites include Achilles tendon insertion site, insertion of the plantar fascia, and lateral epicondyle. Other commonly affected sites include upper and lower poles of the patella, patellar ligament insertion into tibial tuberosity, iliac crests, greater trochanter, and costochondral junctions.[3],[14] Enthesitis was seen in 26.6% of our patients, mainly involving heel and posterior superior iliac spine, which was in consonance with the findings by Malaviya et al. (20%).[11]

Dactylitis is the least common musculoskeletal manifestation of pSpA. It is defined as an increase of more than 10% in the affected digit's circumference compared to the opposite nonaffected digit.[15] Dactylitis involves all compartments of a digit – tenosynovitis, synovitis, soft-tissue edema, and osteitis. The prevalence of dactylitis in pSpA is 40%–49%.[5],[13] We found dactylitis in 30% of patients with pure pSpA, as compared to that of Malaviya et al.[11] (20%) and van der Linden[9] (15.3%).

At least 14% of patients with predominantly peripheral symptoms have a history of IBP, as reported in a study by Rudwaleit et al.[8] Varkas et al.[5] reported IBP in 21% of pSpA patients. Nearly 20% of our cohort of pure pSpA had a past history of IBP. Similar results were reported by de Winter et al., in a recent study in 2019.[3]

Acute anterior uveitis may occur but is relatively uncommon in patients with pSpA.[14] Studies by de Winter et al.[3] and Dougados et al.[6] observed prevalence rates between 2% and 6%. However, none of the patients in the present study had ocular involvement compared with 8% in the study by Malaviya et al.[11]

Almost 90% of axSpA patients are positive for HLA-B27, as per Western literature. Indian studies found the following frequencies of HLA-B27 in patients with SpA: Delhi (92%), Chennai (83%), and Pune (73%).[16] The prevalence of HLA-B27 in predominant pSpA ranges from 27% to 47%.[3] A Latin-American study has also reported a significant association with HLA-B15.[4] We reported HLA-B27 positivity in 80% of our patients with isolated pSpA, which was considerably higher.

Findings of sacroiliitis by plain radiography or magnetic resonance imaging (MRI) may be present in up to 50% of patients with pSpA.[8] Nearly 35% of the patients enrolled in the Clinical REmission in Early peripheral SPondyloArthritis (CRESPA) trial,[13] that also included patients with early pSpA, had sacroiliitis on MRI. Our study observed sacroiliitis in 30% of the patients on radiography, which was higher than the prevalence shown in a previous study from India (Malaviya et al. 16%, all males)[11] but similar to the CRESPA study.[13] This was probably because our center uses SAPA view and not anterior and posterior views for pelvis radiograph because this technique allows X-ray beam to travel down the axis joint and minimizes overlap of the cortices of the lower synovial portion of the articulation, thereby improving visualization.[17] This could have accounted for higher percentages of sacroiliitis in our series. A detailed comparison of the present study, with the previous two studies from India,[8],[10] is given in [Table 2].
Table 2: Comparison of the present study with the two other major studies from India

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Due to the paucity of explicit recommendations for the management of pSpA, current practices rely heavily on European League against Rheumatism (EULAR) recommendations for SpA[18] and EULAR[19] and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis guidelines for psoriatic arthritis,[20] given the similarities in clinical presentations of both these disease entities. In keeping with the guidelines, all our patients received NSAIDs as their initial management. Marzo-Ortega et al. observed that early management with intra-articular glucocorticoids followed by sulfasalazine reduced synovitis faster in early oligoarthritis, after 12 months of treatment, as compared with those initially treated with only NSAIDs.[21] Local peritendinous glucocorticoid injections also benefitted the patients with enthesitis, but only a few studies evaluated its efficacy,[22] and csDMARDS are ineffective for dactylitis and enthesitis.[23] Nearly 66.7% of our patients required csDMARDs in addition to NSAIDs. As regards the efficacy of bDMARDs in pSpA, in the ABILITY-2 study, adalimumab improved the clinical features of the disease and enhanced physical activity in patients with active nonpsoriatic pSpA, who had an inadequate response or intolerance to NSAIDs.[24] ABILITY-2 was the first study to classify nonpsoriatic pSpA patients using ASAS criteria for pSpA, and this was the largest trial of anti-TNFi therapy in this population.[25] More recently, the CRESPA trial[13] studied the effect of golimumab in very early pSpA (≤12-week symptom duration). Nearly 75% of the patients in the pSpA group achieved remission as defined as a complete absence of peripheral arthritis, enthesitis, and dactylitis on clinical examination, compared to 20% of patients with placebo, at week 24.[13] We used a different TNFi in the form of etanercept and infliximab, in our study population, with patients attaining remission.

The strength of our study was that it is only the second study from the Indian subcontinent that strived to look at the clinical, laboratory, and radiologic profile of the pure form of pSpA. Furthermore, it is the only study to have looked at the management profile of pure pSpA patients. Our study also had a few limitations. First, the data were retrospective in nature, and due to the cross-sectional nature of the study, we could not determine causal relationships between the pSpA and other covariates. Second, the sample size was relatively small and data were reported from a single tertiary care military hospital, which may limit its generalization to a larger population. Third, the omission of MRI screening of the SI joint could have accidentally resulted in inclusion of certain cases of nonradiographic SpA.

  Conclusion Top

Pure pSpA is a rare diagnosis amidst the spectrum of peripheral spondyloarthropathies. Patients present with arthritis, enthesitis, or dactylitis without any associated IBD, psoriasis, or preceding infection. Correct and early diagnosis is important as the patients can have favorable outcomes following treatment with csDMARDs and bDMARDS.

Financial support and sponsorship

All the biological agents and investigations were free of cost because the study was carried out in a government hospital.

Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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