A Case of Undifferentiated Connective Tissue Disease with Bilateral Auricular Polychondritis Manifestations: A Rare Clinical Association

Introduction

Undifferentiated connective tissue disease (UCTD) is a complex clinical entity characterized by features suggestive of an autoimmune connective tissue disorder, without fulfilling the comprehensive classification criteria required for a more specific connective tissue disease. The classification criteria for UCTD have been outlined by Mosca et al [1], showing that UCTD is a systemic autoimmune condition that shares clinical and serological features with established connective tissue diseases but does not meet the criteria for definitive diagnosis. The absence of precise classification should not be interpreted as indicative of an overlap syndrome; rather, it reflects the inherently heterogeneous nature of UCTD [2,3].

Recent studies have emphasized that UCTD is an early or incomplete stage of a defined connective tissue disease, with a subset of patients eventually evolving into systemic lupus erythematosus (SLE), systemic sclerosis, or other autoimmune disorders [3,4]. The identification of predictive factors for disease evolution remains an area of active investigation, with autoantibody profiling and clinical phenotyping playing a crucial role in risk stratification

In this report, we describe the case of a 45-year-old man diagnosed with UCTD in 2021, following the classification criteria as detailed by Mosca et al [1]. His disease course was complicated by the onset of polychondritis-like symptoms, providing an example of the diverse and multifaceted presentations of UCTD.

This case underscores the need for heightened clinical awareness of UCTD’s atypical features, as early recognition and appropriate monitoring can facilitate timely intervention and improved long-term outcomes. Furthermore, the recent literature has suggested that novel biomarkers, including specific cytokine signatures and epigenetic modifications, could aid in distinguishing stable UCTD from cases with a higher likelihood of progression [4,5]. The role of interferon signatures, as well as dysregulated B-cell activation, has been increasingly recognized in UCTD patients, providing potential targets for future therapeutic approaches. Emerging therapies, such as B-cell depletion strategies or modulators of interferon pathways, are under investigation to determine whether early intervention in high-risk UCTD cases can alter disease trajectories and prevent progression to more severe autoimmune conditions [5].

Such rare manifestations enrich our understanding of the complexity of UCTD and its potential to exhibit varied autoimmune phenomena. The documentation of such cases is essential for broadening the clinical knowledge base regarding UCTD’s manifestations and for reinforcing the importance of personalized patient management and tailored therapeutic strategies.

Case Report

The patient was a 45-year-old man diagnosed with UCTD in 2021, presenting with acral cyanosis and arthralgias involving the hands, shoulders, and knees. His medical history was otherwise unremarkable, with no previous diagnosis of connective tissue diseases or other autoimmune conditions. The immunological profile revealed a positive antinuclear antibody (ANA) titer of 1: 640 with a speckled pattern, while tests for anti-DNA, extractable nuclear antigens (ENA), anticardiolipin antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA) were all negative. On physical examination, acral cyanosis of the hands was noted along with joint tenderness in the affected areas.

Following diagnosis, treatment was initiated with hydroxychloroquine at 200 mg daily and prednisone at 5 mg daily, which was gradually tapered to 2.5 mg as symptoms stabilized. The patient remained clinically stable until approximately 2 weeks prior to the most recent presentation, when he reported the onset of severe bilateral auricular pain and nodular swelling, particularly affecting the helix of both ears, with greater severity on the left side (Figure 1A, 1B). Physical examination revealed erythematous nodules along the helix, with significant tenderness upon palpation. Given these findings, the prednisone dosage was escalated to 12.5 mg daily, leading to a marked improvement in symptoms, including a reduction in auricular pain and resolution of nodular inflammation.

The patient demonstrated significant clinical improvement following the increase in corticosteroid dosage, with resolution of auricular symptoms and no new manifestations over a 3-month follow-up period. The patient continues to be monitored for any potential recurrence of symptoms or new autoimmune features. The emergence of polychondritis-like symptoms in this patient underscores the dynamic nature of UCTD and the necessity for vigilant monitoring and prompt adjustment of therapeutic interventions. Despite the rarity of polychondritis-like manifestations in UCTD, this case highlights the importance of an individualized approach to treatment, with flexibility to adjust corticosteroid dosing based on evolving clinical findings.

Discussion

The occurrence of polychondritis-like manifestations in UCTD presents a unique clinical challenge, raising questions regarding the underlying immunopathological mechanisms. Small and Frenkiel [6] documented cases of systemic lupus erythematosus (SLE) associated with relapsing polychondritis, suggesting a potential role for localized immune complex deposition as a contributing factor. Similarly, Harisdangkul and Johnson [7] described an association between SLE and relapsing polychondritis, emphasizing the rarity of chondritis in SLE and underscoring the need for vigilant monitoring for other systemic manifestations. These reports support the hypothesis that shared autoimmune mechanisms can predispose patients with UCTD to develop polychondritis-like features.

In the present case, the polychondritis-like involvement was successfully managed with an escalation in corticosteroid therapy, highlighting the responsiveness of these symptoms to immunosuppression. This observation is consistent with prior reports suggesting that corticosteroids are effective in mitigating inflammatory symptoms in cases of relapsing polychondritis associated with connective tissue diseases [8,9].

Nonetheless, corticosteroids alone may not be sufficient in all cases, particularly in patients with relapsing or refractory disease. Immunomodulatory agents, such as methotrexate, azathioprine, or biologic therapies targeting TNF-α or IL-6, have been explored in similar contexts and could be an alternative approach in selected UCTD patients presenting with severe inflammatory manifestations [5,10]. Further research is needed to determine the most effective immunosuppressive regimen in this subset of patients.

Furthermore, the development of polychondritis-like manifestations in UCTD may reflect an evolving autoimmune process, necessitating ongoing clinical vigilance and a tailored approach to immunomodulatory therapy [11,12].

It is also important to distinguish UCTD from other autoimmune conditions that can present with overlapping features, such as SLE or Sjögren’s syndrome. While the immunological profile of this patient did not meet the criteria for a definitive diagnosis of these conditions, the presence of ANA positivity suggests a predisposition to systemic autoimmunity. The absence of specific autoantibodies associated with other connective tissue diseases reinforces the classification of this case as UCTD, albeit with unusual clinical features [13].

The pathogenesis of polychondritis-like manifestations in UCTD remains incompletely understood, but it is plausible that dysregulation of immune pathways common to multiple connective tissue diseases plays a role [14,15].

Recent studies suggest that abnormal activation of the innate immune system, including Toll-like receptors and type I interferon pathways, contribute to the inflammatory cascade observed in these cases [5,10]. This is supported by findings of elevated interferon-stimulated gene expression in patients with early or undifferentiated autoimmune conditions, which could serve as a biomarker for disease activity and progression. Exploring these pathways may provide a deeper understanding of the molecular mechanisms driving UCTD and help identify potential targets for more specific immunomodulatory therapies [16,17].

Future studies exploring the genetic and immunological factors underlying such atypical presentations may provide further insights into the pathophysiology of UCTD and inform more precise therapeutic strategies. Clinicians managing patients with UCTD should be aware of the potential for atypical and evolving manifestations, as early recognition and intervention are key to optimizing patient outcomes.

This case underscores the importance of recognizing the dynamic and potentially evolving nature of UCTD [13]. Personalized, adaptive therapeutic strategies, including the use of corticosteroids, are critical for managing atypical presentations and preventing disease progression. This case report demonstrates that, although rare, polychondritis-like manifestations can occur in UCTD. Moreover, it highlights that a short course of medium-to-low-dose corticosteroid therapy can be an effective treatment strategy for managing these inflammatory features. Further research is warranted to elucidate the immunopathological mechanisms driving such manifestations, with the ultimate goal of improving diagnostic accuracy and therapeutic outcomes in UCTD [18,19].

Conclusions

This case highlights the importance of recognizing atypical manifestations in patients with undifferentiated connective tissue disease (UCTD), particularly those resembling other autoimmune conditions such as polychondritis. Given the heterogeneous nature of UCTD, clinicians must remain vigilant to evolving clinical presentations and be prepared to adjust therapeutic strategies accordingly. The present case demonstrates the efficacy of corticosteroid escalation in managing polychondritis-like manifestations, emphasizing the need for flexible and individualized treatment protocols.

The potential convergence of immunopathological mechanisms between UCTD and other autoimmune diseases adds complexity to the clinical scenario but also offers opportunities for broader therapeutic insights. Understanding these shared pathways could ultimately enhance diagnostic accuracy and improve patient outcomes. Future research focusing on genetic and immunological determinants will be crucial in elucidating the pathogenesis of atypical manifestations within UCTD and optimizing therapeutic approaches. Documenting such cases is essential for expanding the clinical understanding of UCTD, thereby supporting the development of adaptive and comprehensive management strategies that address the full spectrum of clinical presentations.