Bilateral juvenile temporal arteritis: a case-based review

A 40-year-old woman with no significant medical, familial, psycho-social or genetic history was referred to our Unit by her general surgeon for assessment of painless, unilateral nodules on the left temple. Initially presumed to be sebaceous cysts, these nodules had developed gradually over several month. The patient denied headaches, temple allodynia, mandibular pain during mastication, lingual ulcers, visual impairment, or systemic symptoms such as fever, myalgia, weight loss, fatigue, and joint or girdle pain. Physical examination revealed well-circumscribed, painless nodules over the left superficial temporal artery (Fig. 1-A). Notably, the left temporal pulse was attenuated, manifesting pronounced asymmetry compared to the contralateral temporal region. The extra-temple examination was largely unremarkable; no evidence of musculoskeletal, ocular, oral, or cutaneous manifestations was observed. Pulmonary, cardiovascular, and peripheral vascular examinations were normal. The patient’s general physical condition was good, with a body mass index of 21.1 kg/m² and arterial blood pressure recorded at 110/76mmHg, with no appreciable asymmetry between extremities. Abdominal examination revealed no organomegaly, palpable masses, or tenderness. Haematological and biochemical investigations were largely within reference ranges; noteworthy results included a haemoglobin level of 13.7 g/dL, a white blood cell count of 6.5 × 10⁹/L (normal neutrophil, lymphocyte, monocyte, and eosinophil differential counts), and platelet count of 226 × 10⁹/L. APR such as ESR, fibrinogen and CRP were unremarkable. Lactate dehydrogenase (LDH) and SPEP were within expected values. Coagulation tests showed no alterations. Antinuclear antibodies (ANA), ANCA, rheumatoid factor (RF), angiotensin-converting enzyme (ACE) and complement levels (C3 and C4) were negative or normal. Urine sediment exhibited no activity, and proteinuria levels were within normal limits. Chest radiography and electrocardiographic assessments were equally non-contributory. Ultrasonography of the left temple showed hypoechoic regions with some areas showing luminal obliteration, while the axillary artery was unremarkable. Excisional biopsy specimens measuring 1.6 × 0.5 × 0.2 cm and 1.0 × 0.7 × 0.2 cm, respectively, revealed architectural distortion of a medium-sized artery characterised by severe luminal occlusion and intimal thickening. Histopathological analysis confirmed a transmural, dense inflammatory infiltrate predominantly composed of lymphocytes and eosinophils, identifying marked disruptions in the IEL but no GC nor granulomatous formation (Fig. 2A-C). A diagnosis of juvenile temporal arteritis was made.

No treatment was initiated since the nodules initially resolved. During a four-week follow-up, new nodules emerged in both the left (Fig. 1-B) and right temporal regions (not shown), although the patient remained asymptomatic. APR and other biochemical markers persisted stable. Angio-CT scans of the carotid and temporal arteries yielded no significant findings. Although surgical intervention was recommended, the patient chose to undergo a course of CS trial therapy. A new chest X-ray and a QuantiFERON®- TB test were performed, ruling out tuberculosis infection before starting CS. Due to work-related commitments, the patient missed subsequent appointments and neither commenced CS therapy nor underwent surgery. Remarkably, when she returned five months later, the nodules had spontaneously regressed. A twelve-month follow-up confirmed the patient to be asymptomatic with no temporal nodules.

Although often deemed rare, our review suggests bilateral involvement may be more common than acknowledged. Of the 44 examined cases [1, 4, 8, 9, 15‐42], 18 showed bilateral involvement (Table 1), either at diagnosis [4, 16, 18, 20‐22, 25, 28, 30, 33, 38, 41] or during follow-up [35, 36].

Table 2 summarises the main clinical and biological data, treatment modalities, and progression of the cases reviewed. Briefly, the median age of the examined cases was 34.5 years, with a range from 21 to 49 years. A notable difference is observed in the gender distribution, aligning with prior knowledge regarding JTA [4], with males accounting for more than 75% of the patients described [18, 20, 21, 25, 28, 30, 33, 35, 36, 38, 41]. As for presentation, approximately 44.4% of documented cases described the presence of painful nodules [16, 18, 21, 30, 35, 36, 38, 41]. Moreover, a significant 77.8% of cases showed concurrent bilateral involvement (CBI) at diagnosis [4, 16, 18, 20‐22, 25, 28, 30, 33, 38, 41]. In contrast to these typical presentations, our patient initially presented with nodules in the left temple; following a biopsy, there was a recurrence on the left side and new nodules developed on both temples. Similarly, Mikami et al. [36] reported a patient who initially presented with right temple nodules that remained after biopsy and subsequently developed nodules on the left temple that remained and worsened following a biopsy on the left side. In the case described by McGeoch et al. [35], the patient exhibited sequential, rather than concurrent, bilateral temporal involvement: the initial right nodule spontaneously resolved before the emergence of a left temple nodule. In a third case described by Journeau et al. [4]. , the initially biopsied right nodule remained, and a left nodule later developed, increasing the overall CBI occurrence to 83.3%.

Headaches were comparatively infrequent, documented at 28.6% [4, 21, 30, 35, 36]. Other accompanying local symptoms included TB-related scleritis [41], sclerosing sialadenitis [21] and blurred vision [16] with a concurrent history of Raynaud’s phenomenon, though seemingly unrelated. Minor general symptoms were relatively rare, evidenced in 22.2% [21, 35, 36, 38]. While absent in earlier JTA descriptions and present in only 11.4% of Journeau et al. [4]. recent series, their presence should not exclude a JTA diagnosis.

Concerning APR, only two patients (11.1%) showed marginally elevated ESR values [16, 38], implying limited clinical significance.

PBE was noted in 69% of the combined dataset [16, 18, 20, 22, 25, 28, 36, 38], while elevated IgE levels, though less frequently assessed, were present in 66.7% of the reported instances [18, 20, 21, 36].

Histopathology is crucial for the diagnosis of JTA. In our analysis, eosinophilic infiltration was predominant in 94.4% of cases [4, 16, 18, 20‐22, 25, 28, 33, 35, 36, 38, 41], while intimal proliferation or hyperplasia was identified in 77.8% [4, 16, 18, 20, 22, 25, 28, 30, 33, 35], disruption of the internal elastic lamina (IEL) in 44.4% [16, 18, 20, 22, 28, 35, 41] and intraluminal thrombus in 38.9% [18, 21, 22, 30, 35, 36, 38]. Granulomatous lesions or giant cells were anecdotally observed in two cases [18, 41], although described as sparse. These findings highlight the recurrent histopathological features typical of JTA and underline its diagnostic significance.

Contrary to prior literature [8, 38] concerning JTA post-biopsy outcomes, 50% of the considered cases exhibited persistent nodules after biopsy [4, 16, 18, 21, 22, 28, 30, 36], with recurrence in 16.7% [20, 41]. Bilateral involvement can pose a challenge for surgical treatment, as a double biopsy is required and the affected areas are broader, which can lead to cosmetic concerns. Consistent with other reviews [4, 17, 38, 40], no cases progressed to systemic vasculitis, highlighting the benign nature and course of JTA.

Nodule persistence post-biopsy does not suggest a poor prognosis but it certainly compels for a re-evaluation of bilateral JTA management and post-biopsy treatment strategies, although immunosuppressive therapies, unlike in GCA [43], are not the primary approach in JTA. On this subject, when surgical approaches failed or concurrent disorders were present [38], CS therapy was the primary drug choice, given to one-third of patients (33.3%) [20‐22, 36, 38, 41], leading to nodule resolution in more than 65% of them [21, 22, 38, 41]. Beyond CS therapy, several other drugs have been sporadically employed, including colchicine [4], tocopherol nicotinamide [28], aspirin [30], suplatast tosilate [36], and methotrexate (MTX) [20], the latter two being used following CS therapy. In one instance [36], suplatast tosilate (a Th2 cytokine inhibitor, able to block both IL-4 and IL-5 synthesis) was introduced following a brief three-day course of prednisolone (25 mg/day), an inadequate duration to assess the efficacy of CS. In another case, when the initial dose of prednisone at 37.5 mg/d, tapered to 10 mg/d over five months, proved insufficient owing to the continuing presence of painful although regressing nodules, MTX was added to the therapeutic regimen as a steroid-sparing agent [20]. This approach eventually facilitated the discontinuation of both CS therapy and subsequently, MTX.

This review provides insights into JTA by critically evaluating the available clinical and histopathological data, being mindful of the implications of bilateral involvement on patient care. It emphasises the importance of well-defined diagnostic criteria and clarifies treatment strategies for JTA. However, limitations include the small sample size, a retrospective design and the focus on English-only articles, which may limit global representativeness. Differences in diagnostic criteria, treatment and follow-up periods, as well as overlapping features in other conditions (i.e., KD, ALHE, HES), may lead to inconsistent conclusions about the diagnosis, management and progression of JTA, further emphasizing the need for precise diagnostic benchmarks.

Future research on JTA should broaden language inclusion, standardise diagnostic criteria and focus on long-term outcomes, including biopsy impact assessments. Longitudinal studies of JTA cases should explore clinical characteristics, demographic correlations, the impact of early intervention and treatment efficacy, particularly comparing unilateral and bilateral cases. Histopathological analysis may provide insights into the aetiology of JTA, while establishing unified follow-up protocols and evaluation of the efficacy of diagnostic procedures will improve the understanding of the clinical course of the disease.

In our case study, the patient reported her satisfaction with the decision to undergo corticosteroid therapy instead of surgical treatment, a decision supported by the subsequent regression of the nodules. Importantly, the actual administration of corticosteroid therapy was not performed, a detail that emphasises the unpredictable nature of JTA and its potential for spontaneous remission. This case contributes to the ongoing debate about the management of JTA and emphasises the need for a tailored treatment approach that takes into account the individual patient’s condition and the variable progression of the disease. It also highlights the importance of considering conservative management in certain cases, which can lead to favourable outcomes without the risks associated with more invasive treatments.