AbstractBackgroundUpdates on the aetiopathogenesis of acne vulgaris, particularly the inflammatory process, are becoming more and more clear. The TNF superfamily includes tumor necrosis factor (TNF) related weak inducer of apoptosis (TWEAK). It plays a significant part in a variety of inflammatory skin conditions, including psoriasis, alopecia areata and many others. However, its role in acne vulgaris remains questionable.ObjectivesWe aim in this research to evaluate the circulating levels of TWEAK in various severities of acne vulgaris patients and their blood levels before and after oral treatment with isotretinoin.MethodsThis study includes 100 acne vulgaris patients and 100 healthy controls in a case‐control design. All cases, ranging in severity, were treated for 3 months with oral isotretinoin. Enzyme‐linked immunosorbent assay technique was used to measure serum TWEAK before and after 3 months of isotretinoin treatment.ResultsThe serum TWEAK levels were significantly higher in patients than the healthy volunteers (p < 0.001). There were significantly higher serum TWEAK levels with increasing acne vulgaris severity. Additionally, a significant decrease in serum TWEAK level after treatment by oral isotretinoin of AV patients (p < 0.001).ConclusionsTWEAK may play an important role in aetiopathogenesis and the severity of acne vulgaris. Also, oral isotretinoin may target TWEAK in the treatment and alleviate the acne vulgaris.