Orbital Langerhans Cell Histiocytosis: A Systematic Review of 228 Cases

Orbital Langerhans cell histiocytosis (LCH) is an extremely rare disorder, and widely different manifestations often make it diagnostically challenging. The variability of symptoms - from common presentations, such as eyelid swelling and exophthalmos, to very atypical symptoms, like headaches and diplopia - frequently results in delayed diagnosis and mismanagement. This systematic review aims to describe in detail the clinical presentation, diagnostic approaches, treatment modalities, and outcomes of orbital LCH. This systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were conducted in PubMed and Scopus up to August 2024. Synthesis of data involved 228 patients from 18 studies. Extracted data included study design, sample size, patient demographics (age, gender, ethnicity), clinical presentation, diagnostic criteria, treatment modalities, follow-up duration, recurrence rates, and complications. The review found that orbital LCH mostly affects subjects with a mean age of 8.5 years (SD ± 7.1 years), indicating that a greater number of subjects are from younger populations, with 152 males (66.7%) and 76 females (33.3%). The most common presenting symptom was eyelid swelling, reported in 108 patients (47.4%), often serving as the initial sign prompting further investigation, exophthalmos was observed in 95 patients (41.7%), indicating more significant orbital involvement, and palpable mass was detected in 80 patients (35.1%). Imaging played a critical role in the diagnosis, with CT or MRI revealing lytic lesions in nearly all cases (99%). Histopathology confirmed LCH with CD1a and S-100 proteins serving as hallmark markers of LCH. Treatment strategies for orbital LCH varied depending on the extent of disease, patient characteristics, and institutional practices. Surgical intervention was the most common treatment modality, used in 136 patients (59.6%), and it was very effective in localized disease. Radiation therapy was employed in 68 patients (29.8%), often as an adjunct to surgery or as a primary treatment for residual or inoperable disease. Chemotherapy was administered to 85 patients (37.3%), especially those with multisystem involvement. Observation and follow-up were employed in selected cases, particularly those with solitary or asymptomatic lesions, allowing for the possibility of spontaneous regression. Although the remission rate was high, at 79.8%, there was a recurrence in 14.9% of the patients, thus requiring close follow-up. Diabetes insipidus was a complication, and it was also a pointer to multisystem involvement. Orbital LCH is a diagnosis that requires a multidisciplinary approach for accurate diagnosis and effective management, with individualized treatment guided by advanced imaging and molecular markers. Further studies are needed to refine treatment protocols in an attempt to reduce recurrence rates.