Induction cyclophosphamide with maintenance immunosuppression in high-risk myasthenia gravis: long-term follow-up and safety profile.

BACKGROUND: Patients with refractory or high-risk myasthenia gravis (MG) respond poorly to conventional immunosuppressive therapy, requiring rescue therapies and often experiencing treatment toxicity. Rescue and injectable therapies do not induce remission and require repetitive administration leading to significant constraints on patients and the healthcare system. This long-term follow-up study demonstrates cyclophosphamide as a rapidly effective and safe treatment in patients with refractory or high-risk MG. METHODS: Retrospective cohort study of MG patients treated with cyclophosphamide between January 2000 and June 2022 conducted at a quaternary neuroimmunology clinic in New South Wales, Australia. RESULTS: 31 patients were treated: mean age of 64 years; median follow-up 3.6 years (5 months to 11 years); 94% seropositive to acetylcholine receptor (AChR) antibodies and 45% had thymoma. A reduced intensity cyclophosphamide induction protocol followed by oral antiproliferative maintenance is described.Median myasthenia gravis composite scores reduced by >50% after the third cycle of cyclophosphamide. Complete cessation of prednisolone was possible in 11 patients while 20 remained on prednisolone with a median daily dose of 5 mg. Plasma exchange was ceased in 62% of patients and intravenous immunoglobulin ceased in 55%. Cyclophosphamide was generally well tolerated with mild cytopenias. There were no malignancies or cases of haemorrhagic cystitis. CONCLUSION: We describe a large cohort of high-risk MG patients treated with cyclophosphamide in a retrospective single-clinic cohort. We suggest cyclophosphamide should be considered for rapid remission induction, corticosteroid reduction and long-term freedom from recurrent injectable therapies in selected patients, typically those with AChR antibodies.

A systematic review of the clinical outcomes for various orthodontic and physiotherapy appliances used for the management of temporomandibular joint ankylosis.

Ankylosis of the temporomandibular joint (TMJ) is associated with restricted mandibular movements, with deviation to the affected side. The management of TMJ ankylosis involves surgery to mitigate the effects of ankylosis, and adjunctive appliance therapy to supplement the results achieved through surgery. Several appliances have been used to help maintain jaw mobility postsurgery, but have been rarely documented in the literature. Our systematic review aimed to examine the clinical outcomes of various appliances for TMJ ankylosis management. A comprehensive electronic search of the literature was performed in July 2022 to identify eligible articles that had tested the use of orthodontic or physiotherapy appliances for the management of TMJ ankylosis. In total, 13 publications were included in the narrative synthesis. Both generic and custom-made appliances were used, with overall findings suggesting that using these appliances improved mouth opening and reduced chances of re-ankylosis. In this review no universally accepted appliance was found to be utilized, and the criteria used for appliance selection were unclear. The field of research in developing appliances for the treatment of TMJ ankylosis is open to advancement, and this review will help guide future research in this area.

A Giant Silence - An atypical association of sensorineural hearing loss with Giant Cell Arteritis.

Giant cell arteritis (GCA) is a chronic vasculitic disorder predominantly affecting medium to large sized arteries, prevalent in the 50 plus age group. This case illustrates an atypical presentation of this disease in the form of bilateral sensorineural hearing loss (SNHL). Apart from the presence of constitutional and vertiginous symptoms, there were essentially no classical features of GCA. Differentials were broad including infection, malignancy and medication toxicity as well as brain, eye and ear syndromes such as Cogan's syndrome, all of which were eventually excluded. Her diagnosis was ultimately confirmed on positron emission tomography, which highlights the diagnostic importance of this modality. She was managed with corticosteroids then tocilizumab and is making a gradual recovery. Literature review demonstrates that SNHL is more prevalent than previously suggested in GCA, although this does not have widespread recognition. Mechanisms of SNHL in GCA include vascular occlusion, immunological mechanisms including cross reactivity with viral antigens and direct viral infection. SNHL does appear to improve with corticosteroids. This case emphasizes the importance of considering GCA as an important differential in SNHL.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.