Anti-Tumor Necrosis Factor Alpha-Induced Drug Eruptions: One Patient, More Than a Pattern

Background: Tumor necrosis factor alpha (TNFα) antagonists are effective in treating several immune-inflammatory diseases, including psoriasis and inflammatory bowel disease. The paradoxical and unpredictable induction of psoriasis and psoriasiform skin lesions is a recognized adverse event, although of unclear aetiology. However, histological analysis of these eruptions remains insufficient, yet suggesting that some might constitute a new pattern of adverse drug reaction, rather than true psoriasis. Case report: The authors report the case of a 43-year-old woman with severe recalcitrant Crohn disease who started treatment with infliximab. There was also a personal history of mild plaque psoriasis without clinical expression for the past eight years. She developed a heterogeneous cutaneous eruption of psoriasiform morphology with pustules and crusts after the third infliximab infusion. The histopathological diagnosis was of a Sweet-like dermatosis. The patient was successfully treated with cyclosporine in association with both topical corticosteroid and vitamin D3 analogue. Three weeks after switching to adalimumab a new psoriasiform eruption was observed, histologically compatible with a psoriasiform drug eruption. Despite this, and considering the beneficial effect on the inflammatory bowel disease, it was decided to maintain treatment with adalimumab and to treat through with topicals, with progressive control of skin disease. Discussion: Not much is known about the pathogenesis of psoriasiform eruptions induced by biological therapies, but genetic predisposition and Koebner phenomenon may contribute to it. Histopathology can add new facets to the comprehension of psoriasiform reactions. In fact, histopathologic patterns of such skin lesions appear to be varied, in a clear asymmetry with clinical findings. Conclusion: The sequential identification in the same patient of two clinical and histopathologic patterns of drug reaction to TNFα antagonists is rare. Additionally, to the authors’ knowledge, there is only one other description in literature of a TNFα antagonist-induced Sweet-like dermatosis, emphasizing the singularity of this case report.

Analysis of the EEG Dynamics of Epileptic Activity in Gelastic Seizures Using Decomposition in Independent Components

Objective: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. Methods: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. Results: In the two patients with hypothalamic hamartomas consistent ictal delta (2–3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. Conclusions: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. Significance: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.