Systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) are two distinct immunological disorders with different etiopathogenic profiles and their co-existence is very rare. The present study discusses two cases of co-existing AS with SLE. The first case, which fulfilled the criteria for lupus, had HLA-B27 arthritis with predominant peripheral involvement, bilateral hip disease associated with non-scarring alopecia, recurrent oral ulcers and positive immunological markers. The second case was of a 37-year-old male with lupus (predominantly musculoskeletal and cutaneous) who presented with inflammatory low backache. The patient had high titers of ANA and anti-dsDNA positivity and was on methotrexate treatment. On evaluation, he was found to have HLA B27 positivity and bilateral active sacroiliitis. The distinguishing feature of both the cases was that the time frame of presentation of the disorders was almost same, while second case had a significant time frame between the two disorders.

Keywords: ankylosing spondylitis, systemic lupus erythematosus, HLA-B27, arthritis, sacroiliitis

In 2011, a 37-year-old male presented with inflammatory pain in small joints of both hands along with excessive hair fall and recurrent oral ulcerations. His investigations revealed positive ANA (1 in 2560 with 4+ intensity and homogenous pattern) and anti-Smith antibodies. Rheumatoid factor and anti-CCP levels were negative. Complement levels were low and urine protein to creatinine ratio was normal. The patient was started with methotrexate and low-dose steroids (which were tapered and stopped). However, he stopped the medications by himself after 3 years. The lupus flare recurred after 5 years of initial presentation, which was managed with tapering dose of steroids and methotrexate. During the recent presentation, he had inflammatory back pain and right knee joint pain associated with swelling for 2-3 months. Further evaluation revealed raised ESR and CRP levels. Whereas, hemogram, and liver and kidney function tests were normal. The PCR assay for HLA-B27 was positive. MRI of sacroiliac joint was suggestive of active left sacroiliitis and subacute to chronic right sacroiliitis (Fig. 2). The patient was diagnosed as ankylosing spondylitis with SLE and was advised to undergo NSAID therapy for 4 weeks. Biological therapy was also planned if there was no response.

Fig. 2: MRI imaging showing bilateral sacroiliitis

Discussion

Literature review shows that there are only very few cases on co-existence of AS and lupus. The first case reported had non-scaring alopecia, recurrent oral ulcerations, ANA and anti ds-DNA positivity, and low complement levels. On the other hand, the patient fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA such as HLA B-27 positivity, and the presence of arthritis and enthesitis. Most of the reported cases including the present case was noted in females. In most of the cases, the presence of SLE was noted before the occurrence of spondyloarthritis, whereas in the currently reported first case, both the disorders manifested at the same period of time. Clinical findings favoring the diagnosis of spondyloarthritis were pain with inflammatory nature, response to NSAIDS, high inflammatory markers, and MRI evidence of bone marrow edema in bilateral sacroiliac joint.

One contradictory point was the presence of inflammatory back pain, even in SLE patients with lupus. But the presence of associated peripheral joint pain, HLA-B27 positivity and sacroiliitis in MRI made the diagnosis in favor of spondyloarthritis, as the co-existence of these two disorders is very rare. In 1982, Nashel et al. have reported the first case of lupus with SpA in a 43-year-old male patient.¹ Recently in 2020, Nesilhan et al. have studied 281 SLE patients in whom inflammatory back pain was present in 16.3% and sacroiliitis in 7.8%. Only one patient was found to have HLA-B27 positivity.² De Smet et al. described sacroiliitis in 9 patients with active SLE with elevated radionucleotide uptake ratios in sacroiliac joints and further reported that uptake ratios returned to normal in patients who achieved remission.³ Vivas et al. in 1985 reported sacroilitis in 16 male patients with SLE and HLA-B27 negativity was noted in all of the subjects.⁴ In 2019, Enginar reported a case of spondyloarthritis with discoid lupus, with manifestation of both disorders at the same time of presentation.⁵ Another case was reported by Tarhan in 2014, where a patient of SLE (biopsy-proven lupus nephritis) presented with spondyloarthritis manifestations 8 years after diagnosis of SLE^.7 Here the time frame may be comparable to the currently documented second case, but the patient was a young male who was diagnosed initially with lupus and diagnosed with spondyloarthritis after 10 years.

Studies have suggested that the combination of HLA-B27 with HLA-A1 and HLA-DR2, or with HLA-A1 and HLA-DR3 is very rare.¹This finding suggests that apart from HLA association, some other linked pathogenesis exists between these two disorders. Many studies have recently suggested the importance of IL17/23 axis in ankylosing spondylosis pathogenesis. Even though SLE is mainly mediated by interferon pathways, recent studies have shown elevated IL-17 levels in SLE.7 IL-17 can directly stimulate the B cells to produce autoantibodies and is responsible for autoimmune disease process.⁸ Further, some other studies are suggesting that there is recruitment of IL-17 producing T helper cells in kidney, skin and CNS in SLE patients.⁶ These findings indicate that the IL-17 can act as a common gateway for both disorders and further studies are needed to confirm this entity.

Conclusion

The present study highlights the need to consider the probability of co-existence of AS and SLE. The study also emphasizes the time frame of two different disease presentations, one case with two disorders at the same time frame and another case with a significant time gap between two disorders, which can evoke a therapeutic challenge for a treating rheumatologist.