Exploring Anti-TNF Therapy in Relapsing Polychondritis with Co-Existing Ulcerative Colitis: A Case Report and Literature Review

Introduction

Relapsing polychondritis (RP) is a rare autoimmune disease mainly characterized by recurrent inflammation involving the cartilaginous tissues such as ears, nose, joints, tracheobronchial tree, and cartilaginous small airways, which can lead to atrophy and deformity of cartilage. Non-cartilaginous tissues may also be affected, such as the eyes, skin, and aorta. There have not been any randomized therapeutic trials for the management of RP, so the treatment is mainly empirical [1]. The course of the disease is long and often cannot be predicted; it fluctuates between mild auricular or nose inflammation to life-threatening presentations such as cardiovascular or tracheobronchial involvement. It has been recently discovered that some patients diagnosed with RP have somatic mutations in the gene encoding for ubiquitin activating enzyme 1 (UBA1), which causes a well-described syndrome known as Vacuoles, E1 enzyme, X-linked, Autoinflammation (VEXAS) syndrome [2].

The first diagnostic standardized criteria for RP, McAdam’s criteria, specify that a diagnosis requires the presence of any 3 out of the following 6 features: bilateral auricular chondritis, nonerosive seronegative inflammatory arthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, and audiovestibular dysfunction [3].

The goal of therapy is to control the inflammatory process with long-term suppression of immune-mediated inflammatory mechanisms. The ideal therapy should allow the achievement of rapid relief of symptoms and the prevention of multi-organ effects on cartilaginous structures, with the fewest side effects, taking into consideration the need for chronic usage. Non-steroidal anti-inflammatory drugs (NSAIDs) can be initiated for pain control in milder forms of RP, characterized by involvement of nose, external ear, or joints only. Mild manifestations can also be managed by other agents like dapsone or colchicine. In cases that show no improvement, or in severe forms of RP, including ocular, tracheobronchial tree, or cardiac involvement, or if there is evidence of systemic vasculitis or other autoimmune disease, systemic corticosteroids are considered the treatment of choice. Other agents like methotrexate, azathioprine, cyclophosphamide, adalimumab, and other biologics have been introduced empirically to patients with severe forms of RP and good outcomes in terms of disease control and long-term morbidity and mortality have been achieved [4].

Although RP is rare, it can occur in association with autoimmune diseases, especially with inflammatory bowel disease (IBD) like ulcerative colitis (UC). Some studies suggest a shared autoimmune basis, as both diseases involve dysregulation of the immune system and an aberrant inflammatory response [5–7]. Both diseases involve dysfunction of the immune system. In UC, the immune system attacks the colon lining; in RP, it attacks cartilage. They may share common inflammatory pathways (eg, Th17 cells, and cytokines like IL-6 and TNF-α) [5–8].

Case Report

We report the case of a 39-year-old man who was originally from Egypt, had been living with his family in Saudi Arabia for the last 5 years, and had not been known to have any medical illness. He had been referred to the rheumatology clinic from the ophthalmology service in February 2023 as a case of scleritis that was positive for anti-nuclear antibody (ANA), and required further rheumatology evaluation. The patient reported symptom onset in early 2022, when he started noticing recurrent episodes of pain, redness, and swelling in the nose, affecting the quality of his sleep. This episode resolved after 7 days of NSAID treatment. During that time, the patient was seen in the ENT clinic and diagnosed with nasal septal deviation.

In August 2022, the patient had developed right eye pain, redness, photophobia, and eye tenderness. He was seen by an ophthalmologist and he was started on steroids, after which the symptoms resolved completely.

Similarly, in December 2022, the patient started to experience nose and bilateral ear pain, redness, tenderness, and swelling, which resolved after another course of steroids. After stopping the steroids for 1 week, another relapse occurred in form of left eye pain and redness, with new onset of chest tightness associated with on and off shortness of breath with exertion and wheezing.

Reintroducing steroid therapy relieved his symptoms, but withholding steroids caused him to develop another relapse in the form of nose, bilateral ear, and bilateral eye pain and redness, which were resolved with steroids once again. At that point, the patient was started on adalimumab 40 mg every 2 weeks and oral prednisolone 20 mg per day by his primary ophthalmologist. Overall, there was no history of vision loss, nasal discharge, sinusitis, rhinorrhea, epistaxis, ear discharge, vertigo, tinnitus, neck rigidity, decreased appetite, abdominal pain, distension, jaundice, dysphagia, melena, constipation, rashes, Raynaud’s phenomena, or sicca symptoms. No arthritis or arthralgia, mouth or genital ulcers, headache, seizures, loss of consciousness, palpitation, chest pain, syncope, urinary symptoms, fever, weight loss, or night sweats were seen. In addition, the patient had no history of contact with another sick patient or recent travels. After starting the beforementioned therapy, the patient started to have on and off watery diarrhea 5–6 times per day associated with mucus occasionally but no fresh blood or melena. His family history was unremarkable for malignancy or autoimmune diseases, he was fully vaccinated with 3 doses of COVID-19 vaccine, he had no history of allergies or blood transfusion, and his past medical and surgical history were unremarkable. He was a non-smoker with no history of alcoholic ingestion or illicit drug use. On examination, the patient was vitally stable, with unremarkable physical findings except for bilateral ear redness with mild tenderness, and no swelling or discharge (Figure 1A, 1B). On chest auscultation there was normal vesicular breathing with bilateral scattered wheezing. Other systemic examination was unremarkable. Laboratory test results are presented in Table 1. Regarding imaging, chest X-ray and high resolution computed tomography (HRCT) were done and both were unremarkable

The patient was referred to the gastroenterology clinic for evaluation of diarrhea and high levels of fecal calprotectin, and underwent colonoscopy. The colonoscopy showed moderate colitis in the form of erythema and decreased vascular pattern with mild friability. The erythema extended from the rectum to the proximal ascending colon. Multiple biopsies were taken, and they showed chronic inflammation crypt abscesses with crypt architectural distortion (Figure 2A–2D). These findings are consistent with a Mayo 2 score for UC. Diagnosis was conducted by applying McAdam’s criteria for RP, and his case met the following criteria: 1-bilateral auricular chondritis, 2-nasal chondritis, 3-ocular inflammation (conjunctives, keratitis, scleritis/episcleritis, uveitis), 4-respiratory tract chondritis. On the basis of these criteria, this patient was diagnosed with RP in the form of recurrent inflammation of the nose, ears, and eyes, associated with small airway involvement, and he was started on methotrexate 22.5 mg weekly, and oral prednisolone 70 mg per day. He reported improvement in symptoms of RP, but his UC symptoms were still not well controlled. A repeated colonoscopy was done after 4 months, which showed active UC disease. The patient was switched to infliximab. He was given follow-up appointments in the rheumatology clinic for further assessment and medication adjustments, and was directed to the gastroenterology clinic for the UC.

Several months later, his UC subsided completely, after the switch to infliximab treatment for 6 months. It is still unknown whether the patient had subclinical UC that manifested clinically upon the introduction of adalimumab, or, since the literature demonstrates an association of RP with IBD like UC, It could be postulated that UC manifested itself incidentally along with the RP.

Discussion

LIMITATIONS:

As this is a case report, one single patient is not enough to define a clear and scientific conclusion due to the lack of statistical power.

Conclusions

To conclude, both RP and IBD can co-exist simultaneously in some patients. According to the literature, anti-TNF agents are considered promising for the management of cases in which conventional immunosuppressive therapy has failed. In our case, treatment with adalimumab controlled the RP; however, it was not successful in treating the UC symptoms. This raises the question of whether infliximab should be a drug of choice as a TNF-alpha blocker in this situation, as the patient’s UC symptoms subsided completely since the introduction of infliximab. Thus, further research is required to determine standardized treatment guidelines for RP co-existing with IBD, as well as to determine whether or not they have a true association with each other.