Tocilizumab: Another medication related to osteonecrosis of the jaws? A case report and literature review.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients receiving antiresorptive medication, such as bisphosphonates and denosumab, for different oncologic and non-oncologic diseases. Here, we report a case of MRONJ in a patient treated with tocilizumab, a humanized anti-interleukin-6 receptor antibody that effectively treats moderate to severe rheumatoid arthritis in adults. Case description: A 45-year-old female patient diagnosed with severe rheumatoid arthritis, who had been undergoing intravenous tocilizumab therapy for three years without history of bisphosphonate use, was referred to our department. Four weeks previously, several teeth in the maxilla and mandible were removed under local anesthesia by her dentist. Two weeks after the extractions, she felt pain in both jaws. We diagnosed wound dehiscence and delayed healing of the alveolar bone after the tooth extractions. Digital volume tomography showed persistent dry alveolar sockets. The patient underwent surgical debridement of necrotic bone, and intravenous antibiotics were administered in hospital. Five months later, wound dehiscence reoccurred in the same regions. Histopathological analysis of bone biopsies revealed a diagnosis of MRONJ. Four months later, wound dehiscence occurred in the left maxillary alveolar ridge, and local bone resection was performed under antibiotic treatment. Twenty-four months after the last surgery, wound dehiscence had healed completely without signs of recurrence. Discussion: Osteomyelitis of the jaw in patients treated with tocilizumab has not been reported often. This case confirms the potential role of this interleukin-6 receptor inhibitor in the pathogenesis of MRONJ and shows that patients who receive tocilizumab with MRONJ-like symptoms should be closely monitored. The pathomechanism of MRONJ under tocilizumab therapy remains unclear, so dental practitioners, maxillofacial surgeons, and rheumatologists should look for signs of MRONJ in patients receiving tocilizumab to prevent MRONJ onset.

A rare cause for lower back pain: a case of an IgG4-related periaortitis.

IgG4-related disease (IgG4-RD) are a group of autoinflammatory diseases often presenting as tumor-like lesions because of their infiltrative or mass forming behavior. They are characterized by a typical histology consisting of storiform fibrosis, high numbers of infiltrating IgG4-positive plasma cells, obliterative phlebitis, and a moderate presence of eosinophilic cells. Serum IgG4 levels can be elevated. We present a case of a 57 year-old male patient with immobilizing lower back pain, fever, and night sweats. We diagnosed IgG4-related periaortitis using serum IgG4 levels, abdominal ultrasound, PET/CT, and histology. We successfully treated the patient with glucocorticoids (GC) and azathioprine. Periaortitis is a rare presentation of IgG4-RD and therefore noteworthy. It has to be considered in patients with a retroperitoneal mass.

Eruptive Nevi Mimicking Wart-Like Lesions under Selective BRAF Inhibition in a 37-Year-Old Female Melanoma Patient.

BACKGROUND: The BRAF inhibitor vemurafenib is state of the art in therapy of patients with malignant melanoma in non-resectable stage III or stage IV and evidence of oncogenetic BRAF mutation. Multiple cutaneous side effects like rash and keratoacanthoma-like lesions have been described so far. CASE REPORT: We report a patient who presented multiple wart-like lesions under therapy with vemurafenib. Histologically we have seen multiple melanocytic nevi with a wart-like appearance. One melanoma in situ developed on the left forearm. CONCLUSIONS: Eruptive nevi and induction of melanoma may be a further side effect in patients undergoing a therapy with BRAF inhibitors.

Mitomycin-C-treated peripheral blood mononuclear cells (PBMCs) prolong allograft survival in composite tissue allotransplantation.

BACKGROUND: Composite tissue allotransplantation (CTA) was introduced as a potential treatment for complex reconstructive procedures and has become a clinical reality. Hand and face transplantation, the most widely recognized forms of CTA, have intensified immunological research in this emerging field of transplantation. Mitomycin C (MMC) is an alkylating agent that suppresses allogeneic T-cell responses. MMC-treated dendritic cells/PBMCs have been shown to induce donor-specific tolerance in solid organ allograft transplantations. METHODS: Fully mismatched rats were used as hind limb donors [Lewis (RT1(1))] and recipients [Brown-Norway (RT1(n))]. Fifty-five allogeneic hind limb transplantations were accomplished in six groups. Group A (n = 10) received donor-derived MMC-treated PBMCs on transplantation day. Group B (n = 10) rats received no immunosuppression, group C (n = 10) received FK506 and prednisolon, group D consisted in isograft transplantation without immunosuppression, group E (n = 10) received non-treated PBMCs, and group F (n = 5) received PBS without any donor-derived cells. Rejection was assessed clinically and histologically. RESULTS: In group A, the survival times of the allografts were prolonged to an average of 8.0 d. Rejection was significantly delayed compared with the averages of the corresponding control groups B, E, and F (5.5, 5.9, and 5.8 d). No rejection was seen in control groups C and D. CONCLUSION: These results demonstrate that MMC-treated donor PBMCs significantly prolong allograft survival when administered systemically on the day of transplantation. However, the immunomodulatory effect is relatively modest with further research being required to clarify dose-effect relations, cell characteristics, and an optimized mechanism and timing for cell application.

Shock wave treatment in composite tissue allotransplantation.

INTRODUCTION: Composite tissue allotransplantation is a newly emerged field of transplantation. Shock wave technology has already been used in the treatment of urologic and orthopedic disorders. Recent studies demonstrated a suppression of the early proinflammatory immune response. METHODS: 50 allogeneic hindlimb transplantations were performed on rats in 5 different groups. Group A (n = 10), (Lewis → Brown-Norway) received 500 impulses of extracorporeal shock wave. Groups B, C, D, and E served as control groups with group B (n = 10) receiving no immunosuppression, group C (n = 10) receiving FK506 and prednisolone, group D (n = 10) receiving no immunosuppression with isograft transplantations (Brown-Norway → Brown-Norway) and group E receiving 500 impulses of extracorporeal shock wave on the contralateral hindlimb. RESULTS: Rejection of the allogeneic hindlimb occurred on average 7.12 days after transplantation in group A (extracorporeal shock wave). Rejection was significantly delayed compared to the control groups B (no immunosuppression) and E (contralateral hindlimb), where rejection of the allogeneic hindlimb occurred on average 5.49 and 5.6 days after transplantation (t test, P < .01). No rejection was seen in groups C and D. CONCLUSIONS: For the first time, shock waves have been applied in a composite tissue allotransplantation model and resulted in a significant immunosuppressive effect. These promising first results have showed that shock wave treatment is clinically relevant in composite tissue allotransplantation and justify subsequent research to improve the experimental and clinical outcome.

Comparison of six methods for the assessment of ischemia-reperfusion injury in skeletal muscle following composite tissue allotransplantation.

Ischemia/reperfusion (I/R) injury is one of the factors determining tissue survival in replantation and transplantation surgery. However, more than 20 methods have been used to evaluate I/R injury in muscle. The aim of this study was to examine I/R injury in muscle tissue in a model of composite tissue allotransplantation (rat hindlimb transplantation), based on the analyses of six parameters: nitroblue tetrazolium staining (NBT); histology of the anterior tibial and extensor digitorum muscle; wet-to-dry weight ratio; serum potassium; and serum creatine kinase (CK)), in order to identify the most practicable and reliable outcome parameter. Results demonstrated that NBT staining and the wet/dry weight ratio are reliable tools for outcome measurement. The wet/dry weight ratio is the easiest to perform and the authors consider it to be useful for screening purposes. Histologic assessment shows areas of necrosis, but is not a reliable method for semi-quantitative evaluation. Serum potassium and CK levels were higher following transplantation, but they cannot be recommended for assessment purposes, as no significant correlation with other parameters was seen. These findings help further researchers in their selection of reliable outcome parameters to measure I/R injury in skeletal muscle.