Novel observational study protocol to develop a prediction model that identifies patients with Graves’ ophthalmopathy insensitive to intravenous glucocorticoids pulse therapy

IntroductionIntravenous glucocorticoids pulse therapy is the first-line treatment for moderate-to-severe and active Graves’ ophthalmopathy, with a large proportion of patients having poor efficacy and exposed to the risk of glucocorticoids adverse effects. We introduce a novel protocol to develop a prediction model designed to identify patients with Graves’ ophthalmopathy who are not likely to benefit from intravenous glucocorticoids pulse therapy before administration, so that these patients can advance the time to receive appropriate treatment. Existing prediction models for prognosis of Graves’ ophthalmopathy have usually focused on traditional clinical indicators without adequate consideration of orbital soft tissue changes. Our protocol for model development will address this limitation by using artificial intelligence models to quantify facial morphological changes.Methods and analysisThis study is a single-centre, prospective and observational study. A sample size of 278 patients with moderate-to-severe and active Graves’ ophthalmopathy will be prospectively recruited at ophthalmology clinic of Shanghai Ninth People’s Hospital to collect clinical and artificial intelligence model’s baseline data as potential variables to develop the prediction model. They will receive 12-week intravenous glucocorticoids pulse therapy according to the 2021 European Group on Graves’ Orbitopathy treatment guideline. After standard medication course and following 12-week observation, patients will be evaluated for the effectiveness of treatment in our ophthalmology clinic and divided into glucocorticoids-sensitive and glucocorticoids-insensitive groups. The model will be developed by means of multivariate logistic regression to select the best variables for the prediction of glucocorticoids treatment efficacy before administration. The result of the study will provide evidence for the use of a prediction model to personalise treatment options for patients with moderate-to-severe and active Graves’ ophthalmopathy.Ethics and disseminationThe study received approval from the Ethics Committee of Shanghai Ninth People’s Hospital (ethical approval number: SH9H-2020-T211-1. Findings will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberChiCTR2000036584 (Pre-results).

Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.

Beneficial effect of low-dose radioiodine ablation for Graves’ orbitopathy: results of a retrospective study

Objective Graves’ orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. Methods Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. Results The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. Conclusions The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.

Neuromyelitis optica (NMO): treatment during pregnancy

Background: NMO is a demyelinating autoimmune disorder of the CNS which affects the optic nerves and the spinal cord. Method: review based on papers from 2016 to 2020. Platforms used: MEDLINE and Pubmed. The descriptors: “NMO” AND “Treatment”. Objective: to review therapeutic approaches and restrictions for NMO during pregnancy. Case report: G.V.L, 17 years, 23 weeks pregnant, diagnosis of NMO in Dec/2020, with progressive loss of visual acuity and limbs paresthesia. The patient received intravenous methylprednisolone pulses 1g/5 days, followed by 7 sessions of plasmapheresis (PLEX), showing partial symptoms remission, prednisone 60 mg was maintained. March/2021: she presented symptoms reissue, cranial MRI w/o: nerves signal alteration, chiasma and bilateral optical tracts. Spine MRI w/o: slight signal alteration in the dorsal root of the spinal cord, which extends from C1 to C4. Other 5 sessions of PLEX were attempted, without improvement. Results: during pregnancy, intravenous glucocorticoid, Rituximab and Eculizumab proved to be safe in the treatment of NMO. PLEX is indicated in cases of remissions resistant to medications. The therapy with immunosuppressants, such as methotrexate, mycophenolate mofetil and mitoxantrone, isn’t recommended. These immunosuppressants can cause miscarriage or pose a risk to the fetus. However, the immunosuppressant azathioprine has a safety profile in pregnancy; furthermore, it is considered the most appropriate maintenance treatment in combination with prednisone. Conclusion: due to the risk of miscarriage and teratogenicity, NMO treatment during pregnancy is restrict to intravenous glucocorticoids, rituximab and eculizumab, and in specific cases PLEX.

When fever is more than infection: two cases of vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS)

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, but serious systemic hypersensitivity reaction associated with a range of medications. We present two cases of vancomycin-induced DRESS, which occurred simultaneously in the orthopaedic ward in an outer metropolitan hospital. These cases demonstrate the complexity in the diagnosis and management of this inflammatory syndrome on the background of known infection as well as evidence for linezolid as an alternative to vancomycin. The first case was managed conservatively, but developed progressive renal and liver injury along with demonstrated cytomegalovirus reactivation and recurrent colitis, and was eventually palliated. The second was commenced on intravenous glucocorticoids and achieved remission, although had ongoing renal dysfunction at the time of discharge from outpatient follow-up.

En coup de sabre — a case report of therapeutic difficulties

En coup de sabre (ECDS) is a rare linear form of localized scleroderma that occurs more frequently in children than in adults. The involvement of the scalp leads to cicatricial alopecia. The aim of this paper is to present a problematic case of ECDS in young female patient. Many terapeutical methods were introduced, based on guidelines described in diagnostic and therapeutic recommendations of the Polish Dermatological Society (e.g. methotrexate, oral and intravenous glucocorticoids, subcutaneous triamcinolone injections and topical high potent steroids as well as kalcineurin inhibitor (tacrolimus). The lasting improvement was not achieved. The remission was finally induced after the implementation of mycophenolate mofetil.

Fulminant Acute Disseminated Encephalomyelitis: A Remarkable Outcome with Cyclophosphamide

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system which occurs predominantly in the pediatric population. Acute treatment is high-dose intravenous glucocorticoids. Alternative treatment is usually intravenous immune globulin and/or plasma exchange. Fulminant ADEM is rare in children. Only a few cases of cyclophosphamide use in refractory ADEM have been reported. Here, we report a case of a 12-year-old girl with fulminant ADEM who was comatose and improved dramatically after cyclophosphamide administration. Cyclophosphamide treatment should be considered as a therapy in children with fulminant ADEM nonresponsive to standard therapies.

Vaping Is Not Safe: A Case of Acute Eosinophilic Pneumonia following Cannabis Vapor Inhalation

There is a well-established association between inhalational exposures and acute eosinophilic pneumonia (AEP). The most reported exposure is cigarette smoking. Here, we present a case of progressive shortness of breath and nonproductive cough in a college student with no significant medical history, approximately 10 days after inhaling cannabis aerosols on two separate occasions. He was started on empiric antibiotics and bronchodilators without improvement. He was diagnosed with AEP based on peripheral eosinophilia and high-resolution CT image results. He made rapid recovery on intravenous glucocorticoids. Vaping has gained popularity among young adults mainly due to the perception that it is a safe alternative to smoking. This case shows that there may be a false sense of security with vaping. Vaping poses a yet-to-be quantified public health threat, which requires further studies.