Dear Editor, Transverse myelitis (TM) is an uncommon inflammatory condition affecting the spinal cord, causing noncompressive myelopathy.1 Longitudinally extensive TM spans more than 3 segments and affects most of the cord’s cross-section, whereas acute partial TM involves fewer than two segments with asymmetric damage.1 TM can result from postinfectious causes, systemic autoimmune diseases, multifocal central nervous system (CNS) disorders, or be idiopathic.1 However, although TM is rare in systemic lupus erythematosus (SLE) and also uncommon in Sjögren’s syndrome (SS), it represents a severe and serious complication with a poor prognosis.2,3 Here, we describe an atypical case of TM arising from the coexistence of SLE and SS suggestive of an overlap syndrome (OS), that, to our knowledge, has not been documented before. Written consent was obtained from the patient. A 41-year-old female without any notable prior medical conditions presented with progressive heaviness and tingling sensations in both legs, accompanied by back pain. She reported that her symptoms initially began in the right leg and then gradually affected both legs over the course of 1 month. The patient did not exhibit any neurologic symptoms in the upper limbs. On the other hand, she complained of fever (38.8°), asthenia, myalgia, and arthralgia. There were no headaches, visual symptoms, dry syndrome, or dysfunction of bowel and bladder control. Neurologic examination showed difficulty walking without assistance, with reduced muscle strength in the lower limbs, bilateral spastic paresis, exaggerated deep tendon reflexes at the knees and ankles, and a positive Babinski sign. All signs were predominantly observed in the right lower limb. The examinations of the upper limbs and cranial nerves were normal, and there were no signs of sensitive disorder, optic neuritis, or cerebellar dysfunction. The examination of the rest of the system was unremarkable. The brain magnetic resonance imaging (MRI) showed no abnormalities. However, the spinal MRI showed a longitudinal lesion extending from T4 to T10 Figure 1a-c with moderate gadolinium enhancement regarding T5 and T8. Visual evoked potentials were normal in both eyes.Figure 1: Spinal magnetic resonance imaging. (a) T2-weighted sagittal sequence showing continuous hyperintense lesion noted from T4 to T10 with cord swelling (arrows). (b and c) T2-weighted axial sequence indicating intramedullary hyperintensity with transverse extension (arrow)Cerebrospinal fluid sample (CFS) evaluation was clear. The total cell count was at 17/mm3 with lymphocyte predominance. The glucose levels were at 3.94 mmol/L and protein levels at 0.23 g/L. CFS culture was negative for bacterium. However, CSF exhibited a type 4 profile with elevated immunoglobulin G (IgG) index at 0.71. The blood analysis revealed pancytopenia characterized by leukopenia (2300/mm3), microcytic anemia (hemoglobin concentration: 8.7 g/dL and mean corpuscular volume: 59.7 fL), and thrombocytopenia (89,000/mm3). Liver, renal, and thyroid function tests, Coombs test, and coagulation profile were all within normal limits. The patient had a normal 24-h proteinuria level. The angiotensin-converting enzyme was normal. The serum levels of complement C3 and C4 were low. Serology tests for syphilis, Brucella, Borrelia, HIV, hepatitis C virus, and hepatitis B virus were negative. Antimyelin oligodendrocyte glycoprotein and anti-AQP4 were negative. The electrophoresis showed diffuse hypergammaglobulinemia, indicating possible autoimmune conditions. The serology for antinuclear antibody (ANA) returned a positive result of 1/5120. In particular, anti-Ro-52, anti-SSB, anti-double-sDNA, and anti-SSA antibodies were positive. Meanwhile, the antiphospholipid antibodies, anti-Scl70, anti-RNP, anti-Sm, and anti-Jo1 were negative. The Schirmer test and ophthalmologic examination results remained normal. The minor salivary gland biopsy demonstrated focal lymphocytic sialadenitis classified as Grade III according to the Chisholm and Mason scoring system. The thorax–abdomen–pelvis scan showed multifocal cylindrical bronchiectasis. Thus, the diagnosis of SLE and SS were established according to the ACR-EULAR 2019 and 2016, respectively. The SLE disease activity score (SLE-DAS) indicated 41.05, suggesting moderate/severe disease activity Figure 2, and the EULAR SS disease activity index (ESSDAI) was 23, reflecting high SS activity. Integrating the medical history of the patient, symptoms, and examination results, the diagnosis of TM linked to an OS of SLE and SS was confirmed. The patient received a 5-day course of pulse methylprednisolone. Gradual clinical improvement was noted. After 5 days of hospitalization, the patient was discharged, transitioned to oral corticosteroids, and started on hydroxychloroquine. However, she declined to undergo treatment with cyclophosphamide. The 4-year follow-up demonstrated complete improvement.Figure 2: The SLE disease activity score result for our case suggests moderate-to-severe disease activity in systemic lupus erythematosusIn our study, SLE diagnosis followed ACR-EULAR 2019 criteria:4 ANA ≥1/80 accompanied by fever, arthralgia, leukopenia, and thrombocytopenia. SS diagnosis used ACR-EULAR 2016 criteria:5 the presence of focal lymphocytic sialadenitis (focus score ≥1) on labial salivary gland biopsy and the detection of anti-SSA antibodies. The patient met criteria for both, indicating an OS. TM was diagnosed based on symptoms and extensive spinal cord lesions. Absence of spinal radiation, optic neuritis, normal brain MRI, and visual evoked potentials excluded multiple sclerosis and neuromyelitis optica spectrum disorder. No compressive, viral, or fungal causes were found, supporting TM linked to the SS-SLE overlap. TM as a complication of two connective tissue diseases is rarely reported in the literature. Our case is the first to describe this unique association and highlights the importance of considering other autoimmune diseases when SS or SLE is present. Previous reports have described cases of TM associated with SS and primary biliary cholangitis,6 along with case linked to SS and psoriasiform dermatitis.7 TM is more commonly observed in SLE associated with antiphospholipid syndrome, suggesting a thromboembolic mechanism.2 While the pathophysiology of TM during SS and SLE remains not yet fully understood, some theories has been suggested.3,8 The primary pathogenic mechanism of TM in SS may involve immunologically mediated small vessel vasculopathy, resulting in ischemia.8 Possible additional mechanisms involve mononuclear cell invasion of the CNS or vascular injury related to antineuronal antibodies and anti-SSA-Ro.3,8 Moreover, anti-SSB, anti-SSA, and anti-sRNP antibodies were significantly more frequent in SLE patients with TM than those without.9 In our case, all these antibodies were positive, supporting this hypothesis. Considering our results from both the SLE-DAS and ESSDAI activity indices, which indicate moderate to severe activity of SLE and high activity of SS, it can be suggested that the OS of SS and SLE may result in a synergistic effect on the immune and CNS. This is potentially reflected by elevated levels of anti-SSA and anti-SSA-Ro-52, which may contribute to the development of TM. However, while TM was found to be more common when SLE was active (64.8%), it is noteworthy to mention that some cases showed that TM can also occur when SLE is not active (35,1%).10 Another interesting observation in our case is the absence of nephritis or hemolytic anemia. Mehta et al. demonstrated that nephritis and hematologic manifestations occur significantly less often in patients with SLE who develop TM.11 However, the presence of pulmonary involvement in our case might be explained by the current activity of SLE. In fact, bronchiectasis can be seen in 21% of cases with SLE.12 There were no studies exploring the involvement of the respiratory system in SLE associated with TM. For the TM manifestations, TM linked to SS or SLE is similar to TM caused by other factors and develops in a comparable manner.10 Patients with SLE or SS and TM often have mild-to-moderate CSF abnormalities, including lymphocytic pleocytosis, elevated protein, and increased IgG, indicating spinal cord inflammation.2,13 Concerning the spinal MRI, there are no specific imaging findings that are associated with the SS or SLE.2,13 However, consistent with our case, TM is more common in both SS and SLE, with the thoracic spinal level most frequently affected.2,3,6 The most common levels of TM in SS were below T4.3,6 The levels of the lesions were not specified in SLE. The thoracic region of the spinal cord contains blood vessels with smaller diameters, making them more susceptible to thrombosis.14 Meanwhile, since conventional MRI does not detect small-vessel involvement, diagnosing CNS vasculitis is challenging for clinicians. Treatment approaches for TM remain nonstandardized. Typically, the initial strategy involves administering boluses of methylprednisolone and cyclophosphamide during the acute phase, followed by a regimen of oral prednisone and monthly cyclophosphamide infusions for 3–12 months.2,3,6 Recovery usually starts within 8 weeks, with more pronounced improvement observed at 3–6 months and a gradual continuation of recovery over the next 2 years.13 Notably, around 50% of patients achieve full recovery, whereas 29% experience partial recovery.13 SLE-related TM had poorer outcomes compared to SS-related TM.2,3,6,13 In our study, the patient showed complete recovery after corticosteroid therapy and remained relapse-free over a follow-up period of 4 years. Additional research is necessary to evaluate corticosteroid monotherapy against combination treatment with immunosuppressants, aiming to refine management protocols for TM associated with connective tissue disorders and to better patient outcomes. Our case highlights the importance of considering an OS between two connective tissue diseases in patients with TM, especially when other neurological symptoms are absent. This suggests a new perspective for exploring TM causes and underscores the need for clinicians to investigate additional autoimmune diseases when diagnosing a single connective tissue disorder. Author’s contribution First author: Study formulation and design, preparing the initial draft, acquisition of data, and approval of the final version for submission. Second author: Study formulation and design, thoroughly revising the manuscript to enhance essential content, and approval of the final version for submission. Third author: Acquisition of data, preparing the initial draft, and approval of the final version for submission. Fourth author: Acquisition of data, preparing the initial draft, and approval of the final version for submission. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
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