Follicular eruption with folliculotropic lymphocytic infiltrates associated with anti-tumor necrosis factor alpha therapy: Report and study of 3 cases

Background We have encountered three cases of follicular eruptions with folliculotropic infiltrates of non-atypical lymphocytes associated with anti-tumor necrosis factor alpha (TNF-alpha) therapy. Methods Three patients aged 15 to 56 years treated with anti-TNF-alpha therapy (one with adalimumab, and two with infliximab) developed follicular eruptions characterized histopathologically by folliculotropic lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly. Results All three cases were characterized histopathologically by folliculotropic cell infiltrates of non-atypical T (CD3+) lymphocytes with variable follicular exocytosis. Marked reduction in CD7 staining and marked predominance of CD4+ cells over CD8+ cells were observed in 1 and 2 cases, respectively. T-cell receptor (TCR) gene rearrangement studies were monoclonal in 1 case. Discontinuation of anti-TNF-alpha therapy in all three cases, with corticosteroid creams in 1 case, led to complete resolution. Rechallenge with adalimumab in 1 case resulted in exacerbation. Replacement of therapy with non-anti-TNF-alpha biologic agents in 2 cases was not associated with recurrence. Conclusion Follicular eruptions with folliculotropic lymphocytic infiltrates associated with anti-TNF-alpha therapy may show some immunophenotypical variations and/or monoclonal TCR gene rearrangements but lack sufficient cytomorphological features of folliculotropic MF. They may resolve with discontinuation of anti-TNF-alpha therapy.