Neglected reactive arthritis complicated by bilateral hip and temporomandibular joints ankylosis after a suspected tetanus infection: a case report

Reactive arthritis had been reported to occur after various vaccinations, including the tetanus toxoid vaccine; here, we report a case of ankylosing arthropathy suggested to be a complication of missed neglected reactive arthritis after tetanus infection. A healthy 20-year-old woman presented with subtrochanteric right femoral fracture; imaging studies showed bilateral ankylosed hip, kyphoscoliosis, bilateral fused temporomandibular joints, and normal sacroiliac joints bilaterally. Laboratory investigations for a rheumatic or autoimmune disease were all within normal ranges. Detailed history revealed admission of the patient to an ICU unit (1 year before the trauma) for a month as she was diagnosed as having tetanus infection, after which she was unable to walk or feed herself. At the final follow-up, the patient started walking with a moderate limb after having a series of surgeries including femoral fracture fixation, temporomandibular joint excision arthroplasty, and bilateral total hip arthroplasty. Unusual complications after tetanus infection can occur in the form of joint ankylosis, which could be presented after prolonged immobilization possibly due to improper management of reactive arthritis.


Case presentation
A 20-year-old female presented to the emergency department in May 2016 with acute pain and swelling of the right proximal thigh after falling on the ground. Initially, history was obtained regarding the mechanism of trauma and past medical comorbidities. The patient's relatives revealed that in June 2015, the patient had a forearm abscess, which was drained at a local hospital. After about 10 days, she developed an attack of toniccolonic convulsions, upon which she was admitted to the ICU for a month. She was diagnosed as having tetanus (they have no documentation to prove the diagnosis); after discharge from the ICU, the patient had stiffness of both lower limbs with difficulty in walking (became wheelchair-bound) and the inability to mouth feeding (upon which the patient received an endogastric tube for feeding). Initial physical examination in the emergency department revealed an external rotation and shortening of the right lower limb, apparent flexion deformity of the left hip with painless limited movement in all directions, and facial deformity. The patient was stable, and after consultation with a maxillofacial surgeon, a series of imaging studies were obtained in the form of lateral plan radiographs for the cervical and lumbar spine, anteroposterior (AP) radiographs for the pelvis and right hip, and a skull computed tomography (CT) (Fig. 1). The patient was diagnosed as having bilateral locked temporomandibular joints (TMJ), bilateral fused hip, right subtrochanteric femoral fracture, and kyphoscoliosis deformity of the spine.
The patient was transferred to the inpatient ward for consultation with a rheumatologist regarding the patient's history and the atypical affection of the hip joints and spine. He suggested the possibility of a seronegative spondylarthritis; however, laboratory investigations in the form of anti-nuclear antibody, HLA-B27, uric acid, hemoglobin, C3 and C4 complement, alanine aminotransferase, aspartate aminotransferase, sodium, potassium, urea, creatinine, urine analysis, and glucose were all within their normal ranges. Pelvis AP plan radiograph showed normal sacroiliac joints bilaterally. Based on the physical and laboratory examination and the absence of any other possible etiology, the diagnosis was made as post tetanus neglected ReA complicated by bilateral hip and bilateral TMJ bony ankylosis.
On the sixth day post-admission, under nasotracheal intubation, general anesthesia, open reduction and internal fixation (ORIF) for the right subtrochanteric fracture using a 90°condylar blade plate (CBP) was performed (Figs. 1c and 2a). The second team of maxillofacial surgeons performed excision arthroplasty of the TMJ; the surgery went uneventfully. The patient was discharged on the 5th day postoperative.
Follow-up at 2 weeks, 6 weeks, 3 months, and 6 months revealed no complications with fracture union started to be noticed in the serial follow-up radiographs.
At 1 year follow-up, the right subtrochanteric fracture achieved complete union; the patient started assisted weight-bearing and sought advice for having surgery to mobilize both hips; she was advised to have a left total hip arthroplasty (THA) first then to have a staged right THA.
Cementless THA for the left hip was performed in August 2017 using a 36-ceramic head (Fig. 2a). Up to 6 months follow-up; the patient had no complications. In February 2018, the patient was scheduled for a staged right THA; metal removal was performed as the 1st stage (Fig. 2b), and then after 3 months (May 2018), the patient had a right THA (Fig. 2c). At the final follow-up, the radiographs showed an acceptable position of both THA with the progression of the spinal deformity (Fig.  3); however, the patient was satisfied with the results of the surgeries; she is now talking and eating properly and walking without assistance with a moderate limb.

Discussion
Joint ankylosis can be either intra-articular (true) or extra-articular (false); the latter can be bony or fibrous, which may originate as a result of joint surface insult following trauma or infection or as sequelae of prolonged immobilization [11]. In a study by Clavet et al. [9], they reported that about 40% of the patients who were admitted to ICU for more than 2 weeks developed a contracture in several joints, including the hips, if they were not routinely mobilized during ICU admission. Our theory for explaining the current case is that the patient had a tetanus infection upon which she was admitted to the ICU; she probably developed ReA, which was missed and complicated with joint ankylosis (first started as fibrous then converted to bony) due to prolonged immobilization in the ICU; this was concluded after excluding other causes which may lead to the same presentation, mainly the seronegative spondylarthritis commonly occurring as ankylosing spondylitis [12], which was excluded by the normal laboratory investigations as well as the absence of sacroiliac joint affection.
The establishment of a definite diagnosis of ReA is difficult as the condition may pass unnoticed [3], as apart from elevated ESR and CRP during acute febrile illness, there are no specific laboratory tests or biomarkers to confirm the diagnosis [4,13]. In our case, this was the only possible diagnosis that we could reach by exclusion after having a normal laboratory investigation.
Tetanus toxoid, which is a purified preparation of inactivated tetanus toxin [14], had been reported to cause ReA in some patients [6]; the clinical presentation can be asymptomatic; in some cases, oligoarthritis of large joints can occur [4]. Schmitt SK reported that lower extremity joint affection is more common in ReA; in chronic untreated cases, some patients can develop a  clinical picture that mimics ankylosing spondylitis [13]. Post tetanic spine deformity in the form of kyphosis was reported in an old case report by A. G. Quinlan [15]; he explained the occurrence of the deformity by the multiple vertebral crush fractures due to spasmodic hyperextension caused by tetanus. However, in the current case, spinal deformity may had occurred as a compensatory mechanism to the stiff pelvis caused by the bilaterally ankylosed hip [16].
As the vaccine itself is considered an imitation of infection to stimulate the immune response [17], we proposed that the reported mechanism behind the development of ReA after tetanus vaccination [5][6][7][8] is the cause of the joint affection in the current case report. Although the exact mechanism by which vaccination trigger ReA is not fully understood [5], however, some theories were postulated to explain this reaction, as the vaccine itself may trigger reactive events in genetically susceptible individuals as it may resemble a host antigen leading to the activation of an autoimmune response which may be enhanced by HLAB27 [6]; however, the expression of HLAB27 is positive in about 75% of the cases [18]; the rest of the cases may be negative as the finding in the current case report.
The stiffness of the joints may be aggravated by the prolonged recumbency, lack of physiotherapy, and the patient's dependence on nasogastric tube feeding, which may lead to the TMJ immobilization for an extended period. We tried to track the ICU doctors who were responsible for the case while she was admitted to the ICU; however, we failed; we tried to contact the hospital to get any information from the medical reports of the patient; we also failed. As we mainly relied on the history given by the patient family for what occurred from the start of her ICU admission till the appearance in our hospital, we could not decide if the whole condition developed during the ICU stay or it started in the ICU and was aggravated by the negligence of physiotherapy and proper care after the patient was discharged. We reached this "possible" diagnosis by exclusion, as this was the most probable scenario in light of all the information collected.

Conclusion
ReA can occur as a complication of tetanus infection with large joint affection, which, if not correctly discovered and treated, could be complicated by joint ankylosis which may be aggravated by prolonged immobilization.