Manifestation of acute appendicitis as known but paradox visceral side effect of ulcerative colitis anti-inflammatory therapy with januskinase-inhibitor Tofacitinib (Xeljanz (TM))

Background:The etiopathogenesis of accompanying inflammatory phenomena and consequences of immunomodulation constitute a challenging and innovative field in the medical treatment of patients with autoimmune diseases. Aim:Based on i) clinical management experience gained from this challenging clinical case and ii) selective references of reports published in the scientific medical literature, we present an unusual counterfactual scientific case report. A patient diagnosed with ulcerative colitis undergoing januskinase (JAK)-inhibitor therapy developed acuteappendicitis as an unusual complication or as a visceral side effect of immunosuppressive/antiinflammatory therapy. Method:Scientific case report. Results:(case description): Medical history: A 52-year-old male presented with spasmodic pain in the right lower abdomen lasting for two days (no fever, no bowel movement changes (no stool irregularities), no vomiting). Medication used to date: Steroid-resistant ulcerative colitis treated with immunosuppressive therapy (Adalimumab administered for 10 months [next generation anti-TNF & alpha; mAb], Vendolizumab for 9 months [& alpha;4 & beta;7 integrin antagonist], Tofacitinib for 6 months); fructose intolerance, no previous abdominal surgery; medication: XeljanzTM (Tofacitinib, 5 mg 2x1; JAK-inhibitor; PFIZER PHARMA GmbH, Berlin,Germany); MutaflorTM (1x1; Ardeypharm GmbH, Herdecke, Germany). Clinical findings:Pressure pain in the right lower abdomen with local muscular defense (Mc-Burney's/Lanz's point positive), no peritonism, Psoas-muscle sign positive. Diagnostic measures: Laboratory parameters: standard value of white blood cell count, CrP: 25 mg/l.-Transabdominal ultrasound revealed hypertrophic 'appendix vermiformis' with detectable target-phenomenon and surrounding fluid. Decision-making:Indication for laparoscopic exploration. Therapy:Under perioperative single-shot antibiotic administration with UnacidTM, the patient underwent emergency laparoscopic appendectomy due to confirmed acute appendicitis with additional lavage and placement of local drainage. Clinical course:The postoperative phase was uneventful (sufficient analgetic therapy, removal of local drainage on the 2nd postoperative day). The patient was discharged four days after surgery. Histopathology confirmed ulcero-phlegmonous, acute purulent appendicitis with fibrinous purulent mesenteriolitis. Further measures:Immunosuppressive therapy was continued. Conclusion:Based on the paradoxon of an acute inflammatory disease (acute appendicitis) seen in the case of a patient undergoing immunosuppressive/anti-inflammatory treatment using a JAK-Inhibitor for ulcerative colitis, we consider this case worthy of publication although this side effect has previously been described in patients with rheumatoid arthritis. This might be the manifestation of i) an immunomodulatory effect that reduced or at least altered mucosal defense, including an increased risk of opportunistic infections, presenting as a specific visceral 'side effect' of the JAK-Inhibitor and/or as a consequence; ii) an induced alternative inflammatory mechanism/proinflammatory signal transduction and -theoretically -an intestinal drainage defect in the segment of right colic artery with consecutive collection of necrotic cells and activation of inflammatory mediators.