Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Abstract

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.