Rifamycin-based regimens are increasingly used for the management of patients with tuberculosis infection because of lower rates of hepatic adverse drug reactions and higher completion rates than other regimens.
Rifampin-induced flu-like syndrome is usually a mild illness associated with intermittent dosing regimens (i.e., weekly) but can also occur with low-dose daily administration.
Mild flu-like symptoms can be managed by short-term, over-the-counter analgesia.
If treatment is temporarily stopped because of flu-like syndrome, patients can uncommonly have a more severe reaction, including shock, after resuming treatment.
Patients should be encouraged to resume treatment in a location where medical care is available in case life-threatening symptoms develop.
A 15-year-old girl, born in a country with a high burden of tuberculosis (TB), was in the care of a tertiary care infectious disease clinic for TB infection (TBI) based on a positive QuantiFERON gold test. She had no evidence of TB disease. She had a history of iron deficiency anemia (hemoglobin 97–104 [normal 112–151] g/L) and moderately active systemic lupus erythematosus (SLE), given her symmetric nonerosive polyarthritis, nonscarring alopecia, photosensitivity and Raynaud phenomenon, as well as positivity for antinuclear, anti-Smith and anti-ribonucleoprotein antibodies. Her medications were naproxen (375 mg, twice daily) and hydroxychloroquine (5.5 mg/kg/d); she had not taken corticosteroids for several years. The patient began treatment with 600 mg rifampin (10 mg/kg/d) and tolerated the medication well for 11 days. For the next 3 days, she had chills and myalgias that began a few hours after rifampin ingestion and resolved a few hours later. She stopped treatment for 3 days without symptom recurrence.
After an in-person assessment, with a normal physical examination aside from arthritis in 2 joints, the patient was advised to resume rifampin. Within 1 hour of taking the medication, she developed sudden onset severe neck pain, myalgias, arthralgias, shortness of breath and chest pain. During ambulance transport to the emergency department, she received a fluid bolus for hypotension (80/40 mm Hg). On physical examination, she was febrile (38.3°C), tachypneic (28 breaths/min, 99% saturation) and tachycardic (123 beats/min) with a low-to-normal blood pressure (91/52 mm Hg). Her weight was 60 kg. She had no angioedema, rash, wheezing or gastrointestinal symptoms. She received intravenous fluids and empiric vancomycin and ceftriaxone. Three hours after symptom onset, she became hypotensive again (89/36 mm Hg) and diaphoretic, requiring fluid resuscitation and norepinephrine and epinephrine infusions. She was admitted to the intensive care unit (ICU).
On physical examination, the patient had no rash or mucous membrane involvement. Blood work showed a decreased leukocyte count at admission (2.84 [normal 4.23–9.99] × 109/L), which increased to 17.34 × 109/L 6 hours later, with low eosinophil counts throughout (0.00 [normal 0.02–0.51] × 109/L). Her hemoglobin level decreased to 74 g/L on the second day of admission after fluid resuscitation. Her bilirubin and haptoglobin levels were normal, a direct antiglobulin test was negative and her blood film did not show schistocytes.
Inflammatory markers were elevated, with a C-reactive protein (CRP) level of 13.6 (normal < 1.7) mg/L at admission, increasing to 101.8 mg/L about 24 hours later. The patient’s aspartate aminotransferase level increased from 71 (normal < 31) U/L to 99 U/L during this time. Her complement C3 level was slightly decreased at 0.76 (normal 0.83–1.52) g/L and her C4 level remained within normal range. Her creatinine kinase level was normal. Given a previous finding of a partially empty sella turcica on magnetic resonance imaging, the patient’s cortisol level was tested and found to be increased at 605 nmol/L (normal range 30–254 nmol/L for evening sampling).
Given the presence of severe neck pain, nuchal rigidity and shock, the critical care team suspected sepsis and performed additional investigations. A computed tomography (CT) scan of the head and an echocardiogram were normal; CT angiography of the neck did not show an infected thrombus or edematous retropharyngeal soft tissue but showed localized myositis. A chest radiograph showed mild pulmonary edema attributed to fluid resuscitation, which responded to diuresis; CT imaging of the lungs showed bilateral increased septal thickening with ground glass opacities. All infectious work-up — including cultures of blood, sputum, throat and cerebrospinal fluid samples, and serology for Epstein–Barr virus, cytomegalovirus and mycoplasma — was negative. The patient was negative for SARS-CoV-2 on polymerase chain reaction.
Because infection was suspected, she received 1 dose of rifampin in the ICU, which led to a decreased blood pressure of 93/39 mm Hg. In response, her vasopressor dose was increased for 6 hours (norepinephrine 0.04–0.06 μg/kg/min). Rifampin was stopped, and the patient was weaned off vasopressors within 30 hours of admission. Our teams became involved after this episode, and we attributed her presentation to a rifampin-induced adverse drug reaction. We started her on isoniazid for TBI and she successfully completed 9 months of therapy. We told her to avoid rifamycin-based medications in the future.
Discussion
Rifampin-induced flu-like syndrome is a type III hypersensitivity reaction that typically develops 1–4 hours after ingestion of a dose, but delayed reactions up to 8–12 hours later have been reported. Symptoms usually last for 8 hours and often include fever, chills, malaise, headache and arthralgias. When treatment is resumed after stopping because of adverse drug reactions, patients may uncommonly develop hypotension and shock, which generally resolve within 24 hours.1–6 The terminology in the literature is inconsistent; we refer to this severe clinical presentation as rifampin-induced flu-like syndrome with shock.
Rifampin-induced flu-like syndrome has been reported for all rifamycin compounds, the drug class to which rifampin belongs.1,2,4 The pathophysiology remains unclear, but the occurrence of this syndrome has been associated with the presence of anti-rifampin antibodies. Because patients may be symptomatic in the absence of anti-rifampin antibodies, and antibodies have been found in patients tolerating rifampin, measurement of antirifampin antibodies is not helpful in the diagnosis or management of this condition.1,3 The diagnosis can be made based on a clinical assessment of presenting symptoms, physical examination and available laboratory investigations, and exclusion of other causes.
Female sex and increasing age have been shown to increase the likelihood of rifampin-induced flu-like syndrome.7 Patients with HIV have been found to have a lower risk;8 however, SLE or other autoimmune diseases have not been reported as risk factors for the development or severity of rifampin-induced flu-like syndrome.9 Treatment-specific risk factors include prolonged treatment duration (i.e., > 3 mo), intermittent dosing (i.e., once weekly) and increased dose (although there is no clear definition for what constitutes an increased dose in this context); however, patients can develop the syndrome without these risk factors.10
Our patient’s presentation was typical for an adverse drug reaction to rifampin, although it was important to consider alternative diagnoses. Infections were excluded, and her clinical presentation was atypical for an SLE flare. She had no signs of pulmonary embolus to explain the hypotension, nor serositis or hemophagocytic syndrome to explain the increased CRP, which is unusual in an SLE flare. Our patient did not have adrenal insufficiency, which can present with hypotension and shock. A Jarisch–Herxheimer reaction that could cause a flu-like syndrome has not been reported in TBI without disease. Although a relatively acute onset of hypotension can suggest anaphylaxis, a pure type I hypersensitivity reaction was unlikely, given the associated symptoms such as fever and raised inflammatory markers. Finally, she had no thrombocytopenia, hemolysis or acute renal failure, which are all uncommon adverse drug reactions to rifamycins.1,2
The Canadian TB Standards strongly endorse 2 rifamycin-based regimens as the preferred treatment of TBI, namely daily rifampin for 4 months or 12 weekly doses of rifapentine (a long-acting rifamycin) and isoniazid.11 These regimens have the advantage of decreasing hepatic adverse drug reactions compared with 9 months of daily isoniazid treatment, and are associated with higher completion rates.12 Among patients receiving the rifapentine regimen for TBI, around 3.5% develop a flu-like reaction;12 a minority (0.2%) develop hypotension requiring intravenous fluid therapy and, occasionally, vasopressors. The rate of flu-like syndrome with the daily rifampin regimen is not reported, but it is thought to be rare.13 Based on the updated treatment recommendations in the Canadian TB Standards, we expect increased usage of rifamycin compounds for TBI in Canada, which will likely result in a higher absolute number of patients with rifamycin-induced adverse drug reactions, particularly rifampin-induced flu-like syndrome. Management guidelines for TBI and TB disease should be updated to provide specific guidance regarding patient counselling and rechallenge with rifamycins.9,13 We suggest that patients should be advised to speak to their prescribing provider if experiencing a possible adverse drug reaction to a rifamycin-based medication to limit unnecessary treatment interruptions. If treatment is stopped because of an adverse drug reaction, patients should discuss when to restart treatment with their provider. Patients who develop a mild flu-like syndrome on weekly rifapentine treatment may tolerate a daily rifampin regimen.1,2,5 Patients on daily rifampin treatment who develop mild flu-like symptoms can be treated with over-the-counter anti-pyrectic and analgesic agents. However, the effectiveness of these treatments is not known. If rifamycin-based therapy is resumed after stopping because of flu-like symptoms, there is a very small risk the patient will develop a more severe reaction.2 Providers should consider the accessibility of appropriate care (e.g., intravenous fluid administration) when planning treatment restart. Intramuscular epinephrine should be considered when intravenous vasopressors are unavailable, although no data regarding its effectiveness are available. For patients who tolerate rifamycin-based treatment upon rechallenge, an observation period of 1 hour appears reasonable based on the available literature. For patients who have had a severe reaction, rifamycin compounds should be avoided. In cases where no alternative treatment is available (e.g., isoniazid drug resistance), rifamycin-based treatment should be resumed under the guidance of a provider experienced in the management of this severe adverse drug reaction. No data are available regarding the success of desensitization for flu-like syndrome.
Given better overall safety and completion rates, rifamycin-based regimens are now the preferred therapy for TBI. It is important that health care providers recognize flu-like symptoms caused by rifamycin compounds, appropriately counsel patients before starting treatment and consider accessibility of appropriate care in case of rechallenge, if the medication has been stopped for this reason.
The section Cases presents brief case reports that convey clear, practical lessons. Preference is given to common presentations of important rare conditions, and important unusual presentations of common problems. Articles start with a case presentation (500 words maximum), and a discussion of the underlying condition follows (1000 words maximum). Visual elements (e.g., tables of the differential diagnosis, clinical features or diagnostic approach) are encouraged. Consent from patients for publication of their story is a necessity. See information for authors at www.cmaj.ca.
Footnotes
Competing interests: None declared.
This article has been peer reviewed.
The authors have obtained patient consent.
Contributors: All of the authors contributed to the conception and design of the work. Gousia Dhhar and Jeanine McColl drafted the manuscript. All of the authors revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
Skinstitut Holiday Gift Kits take the stress out of gifting
Toronto, October 31, 2024 – Beauty gifts are at the top of holiday wish lists this year, and Laser Clinics Canada, a leader in advanced beauty treatments and skincare, is taking the pressure out of seasonal shopping. Today, Laser Clincs Canada announces the arrival of its 2024 Holiday Gift Kits, courtesy of Skinstitut, the exclusive skincare line of Laser Clinics Group.
In time for the busy shopping season, the limited-edition Holiday Gifts Kits are available in Laser Clinics locations in the GTA and Ottawa. Clinics are conveniently located in popular shopping centers, including Hillcrest Mall, Square One, CF Sherway Gardens, Scarborough Town Centre, Rideau Centre, Union Station and CF Markville. These limited-edition Kits are available on a first come, first served basis.
“These kits combine our best-selling products, bundled to address the most relevant skin concerns we’re seeing among our clients,” says Christina Ho, Senior Brand & LAM Manager at Laser Clinics Canada. “With several price points available, the kits offer excellent value and suit a variety of gift-giving needs, from those new to cosmeceuticals to those looking to level up their skincare routine. What’s more, these kits are priced with a savings of up to 33 per cent so gift givers can save during the holiday season.
There are two kits to select from, each designed to address key skin concerns and each with a unique theme — Brightening Basics and Hydration Heroes.
Brightening Basics is a mix of everyday essentials for glowing skin for all skin types. The bundle comes in a sleek pink, reusable case and includes three full-sized products: 200ml gentle cleanser, 50ml Moisture Defence (normal skin) and 30ml1% Hyaluronic Complex Serum. The Brightening Basics kit is available at $129, a saving of 33 per cent.
Hydration Heroes is a mix of hydration essentials and active heroes that cater to a wide variety of clients. A perfect stocking stuffer, this bundle includes four deluxe products: Moisture 15 15 ml Defence for normal skin, 10 ml 1% Hyaluronic Complex Serum, 10 ml Retinol Serum and 50 ml Expert Squalane Cleansing Oil. The kit retails at $59.
In addition to the 2024 Holiday Gifts Kits, gift givers can easily add a Laser Clinic Canada gift card to the mix. Offering flexibility, recipients can choose from a wide range of treatments offered by Laser Clinics Canada, or they can expand their collection of exclusive Skinstitut products.
Brightening Basics 2024 Holiday Gift Kit by Skinstitut, available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.
Hydration Heroes 2024 Holiday Gift Kit by Skinstitut – available exclusively at Laser Clincs Canada clinics and online at skinstitut.ca.
LONDON (AP) — Most people have accumulated a pile of data — selfies, emails, videos and more — on their social media and digital accounts over their lifetimes. What happens to it when we die?
It’s wise to draft a will spelling out who inherits your physical assets after you’re gone, but don’t forget to take care of your digital estate too. Friends and family might treasure files and posts you’ve left behind, but they could get lost in digital purgatory after you pass away unless you take some simple steps.
Here’s how you can prepare your digital life for your survivors:
Apple
The iPhone maker lets you nominate a “ legacy contact ” who can access your Apple account’s data after you die. The company says it’s a secure way to give trusted people access to photos, files and messages. To set it up you’ll need an Apple device with a fairly recent operating system — iPhones and iPads need iOS or iPadOS 15.2 and MacBooks needs macOS Monterey 12.1.
For iPhones, go to settings, tap Sign-in & Security and then Legacy Contact. You can name one or more people, and they don’t need an Apple ID or device.
You’ll have to share an access key with your contact. It can be a digital version sent electronically, or you can print a copy or save it as a screenshot or PDF.
Take note that there are some types of files you won’t be able to pass on — including digital rights-protected music, movies and passwords stored in Apple’s password manager. Legacy contacts can only access a deceased user’s account for three years before Apple deletes the account.
Google
Google takes a different approach with its Inactive Account Manager, which allows you to share your data with someone if it notices that you’ve stopped using your account.
When setting it up, you need to decide how long Google should wait — from three to 18 months — before considering your account inactive. Once that time is up, Google can notify up to 10 people.
You can write a message informing them you’ve stopped using the account, and, optionally, include a link to download your data. You can choose what types of data they can access — including emails, photos, calendar entries and YouTube videos.
There’s also an option to automatically delete your account after three months of inactivity, so your contacts will have to download any data before that deadline.
Facebook and Instagram
Some social media platforms can preserve accounts for people who have died so that friends and family can honor their memories.
When users of Facebook or Instagram die, parent company Meta says it can memorialize the account if it gets a “valid request” from a friend or family member. Requests can be submitted through an online form.
The social media company strongly recommends Facebook users add a legacy contact to look after their memorial accounts. Legacy contacts can do things like respond to new friend requests and update pinned posts, but they can’t read private messages or remove or alter previous posts. You can only choose one person, who also has to have a Facebook account.
You can also ask Facebook or Instagram to delete a deceased user’s account if you’re a close family member or an executor. You’ll need to send in documents like a death certificate.
TikTok
The video-sharing platform says that if a user has died, people can submit a request to memorialize the account through the settings menu. Go to the Report a Problem section, then Account and profile, then Manage account, where you can report a deceased user.
Once an account has been memorialized, it will be labeled “Remembering.” No one will be able to log into the account, which prevents anyone from editing the profile or using the account to post new content or send messages.
X
It’s not possible to nominate a legacy contact on Elon Musk’s social media site. But family members or an authorized person can submit a request to deactivate a deceased user’s account.
Passwords
Besides the major online services, you’ll probably have dozens if not hundreds of other digital accounts that your survivors might need to access. You could just write all your login credentials down in a notebook and put it somewhere safe. But making a physical copy presents its own vulnerabilities. What if you lose track of it? What if someone finds it?
Instead, consider a password manager that has an emergency access feature. Password managers are digital vaults that you can use to store all your credentials. Some, like Keeper,Bitwarden and NordPass, allow users to nominate one or more trusted contacts who can access their keys in case of an emergency such as a death.
But there are a few catches: Those contacts also need to use the same password manager and you might have to pay for the service.
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Is there a tech challenge you need help figuring out? Write to us at onetechtip@ap.org with your questions.
The Canadian Paediatric Society says doctors should regularly screen children for reading difficulties and dyslexia, calling low literacy a “serious public health concern” that can increase the risk of other problems including anxiety, low self-esteem and behavioural issues, with lifelong consequences.
New guidance issued Wednesday says family doctors, nurses, pediatricians and other medical professionals who care for school-aged kids are in a unique position to help struggling readers access educational and specialty supports, noting that identifying problems early couldhelp kids sooner — when it’s more effective — as well as reveal other possible learning or developmental issues.
The 10 recommendations include regular screening for kids aged four to seven, especially if they belong to groups at higher risk of low literacy, including newcomers to Canada, racialized Canadians and Indigenous Peoples. The society says this can be done in a two-to-three-minute office-based assessment.
Other tips encourage doctors to look for conditions often seen among poor readers such as attention-deficit hyperactivity disorder; to advocate for early literacy training for pediatric and family medicine residents; to liaise with schools on behalf of families seeking help; and to push provincial and territorial education ministries to integrate evidence-based phonics instruction into curriculums, starting in kindergarten.
Dr. Scott McLeod, one of the authors and chair of the society’s mental health and developmental disabilities committee, said a key goal is to catch kids who may be falling through the cracks and to better connect families to resources, including quicker targeted help from schools.
“Collaboration in this area is so key because we need to move away from the silos of: everything educational must exist within the educational portfolio,” McLeod said in an interview from Calgary, where he is a developmental pediatrician at Alberta Children’s Hospital.
“Reading, yes, it’s education, but it’s also health because we know that literacy impacts health. So I think that a statement like this opens the window to say: Yes, parents can come to their health-care provider to get advice, get recommendations, hopefully start a collaboration with school teachers.”
McLeod noted that pediatricians already look for signs of low literacy in young children by way of a commonly used tool known as the Rourke Baby Record, which offers a checklist of key topics, such as nutrition and developmental benchmarks, to cover in a well-child appointment.
But he said questions about reading could be “a standing item” in checkups and he hoped the society’s statement to medical professionals who care for children “enhances their confidence in being a strong advocate for the child” while spurring partnerships with others involved in a child’s life such as teachers and psychologists.
The guidance said pediatricians also play a key role in detecting and monitoring conditions that often coexist with difficulty reading such as attention-deficit hyperactivity disorder, but McLeod noted that getting such specific diagnoses typically involves a referral to a specialist, during which time a child continues to struggle.
He also acknowledged that some schools can be slow to act without a specific diagnosis from a specialist, and even then a child may end up on a wait list for school interventions.
“Evidence-based reading instruction shouldn’t have to wait for some of that access to specialized assessments to occur,” he said.
“My hope is that (by) having an existing statement or document written by the Canadian Paediatric Society … we’re able to skip a few steps or have some of the early interventions present,” he said.
McLeod added that obtaining specific assessments from medical specialists is “definitely beneficial and advantageous” to know where a child is at, “but having that sort of clear, thorough assessment shouldn’t be a barrier to intervention starting.”
McLeod said the society was partly spurred to act by 2022’s “Right to Read Inquiry Report” from the Ontario Human Rights Commission, which made 157 recommendations to address inequities related to reading instruction in that province.
He called the new guidelines “a big reminder” to pediatric providers, family doctors, school teachers and psychologists of the importance of literacy.
“Early identification of reading difficulty can truly change the trajectory of a child’s life.”
This report by The Canadian Press was first published Oct. 23, 2024.
