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Hypertrophic herpes simplex virus 2 infection resistant to acyclovir in an immunosuppressed patient



An 80-year-old man on ruxolitinib for myelofibrosis was referred to the infectious diseases clinic with a subacute, progressive mass over his left forehead. He also had type 2 diabetes mellitus and dyslipidemia, and was taking rabeprazole, simvastatin and metformin.

Three years before presentation, he developed an erythematous, crusting rash over the outer side of his left ear. He was previously given a diagnosis of otitis externa, but the rash did not improve despite 14 empiric courses of oral antibacterial therapy. A swab from the lesion was sent for herpes simplex virus (HSV) testing by polymerase chain reaction (PCR), which was positive for HSV-2. The patient had no history of oral or genital HSV infection. The rash resolved with a 5-day course of oral valacyclovir (1 g, 3 times daily). Over the following 3 years, the patient had 8 recurrences involving the left side of his face. These were presumed to be episodes of HSV-2 reactivation and each resolved with empiric oral valacyclovir for 7–10 days.

Six months before presentation, the patient developed a small, sessile, sesame seed–shaped lesion over his left forehead. Despite 18 courses of oral valacyclovir and 3 courses of oral famciclovir (500 mg, twice daily), each for 7–14 days, the mass continued to increase in size. A biopsy was performed, and viral culture was positive for HSV-2. Histopathology showed acantholytic keratinocytic cells with viral changes, suggestive of an ulcerative lesion of viral etiology.

When we saw the patient in clinic, he had a fungating, verrucous mass on his left forehead measuring about 12 × 8 cm and extending superiorly to the scalp (Figure 1). The mass was raised and pink, with a well-demarcated border. It had regions of slough and crusting, but was not tender. The mass and associated edema resulted in slight left-sided ptosis. The patient had no other cutaneous lesions on the head and neck. Cranial nerve examination was normal. Laboratory investigations showed leukocytosis and anemia that were caused by his myelofibrosis (leukocyte count 17.1 [normal 4–11] × 109/L and hemoglobin 95 [normal 120–160] g/L). His creatinine was 92 (normal 42–102) μmol/L.


<a href=”″ title=”A large fungating and verrucous lesion on the left forehead of an 80-year-old man, caused by herpes simplex virus 2 infection; the lesion was progressive over a 6-month period.” class=”highwire-fragment fragment-images colorbox-load” rel=”gallery-fragment-images-684742817″ data-figure-caption=”

A large fungating and verrucous lesion on the left forehead of an 80-year-old man, caused by herpes simplex virus 2 infection; the lesion was progressive over a 6-month period.

” data-icon-position data-hide-link-title=”0″>Figure 1:

Figure 1:

A large fungating and verrucous lesion on the left forehead of an 80-year-old man, caused by herpes simplex virus 2 infection; the lesion was progressive over a 6-month period.

Based on the patient’s history, including multiple previous courses of antiviral treatment, our presumptive diagnosis was hypertrophic HSV infection, with concern for resistance to acyclovir and related compounds (valacyclovir and famciclovir), as evidenced by the lack of clinical response. We obtained a swab of the mass for HSV PCR, which was positive for HSV-2. Genotyping was performed at the National Microbiology Laboratory in Winnipeg. Sequence variations in the UL23 thymidine kinase gene were identified, confirming resistance. Testing for HIV was negative.

We treated the patient with intravenous foscarnet (90 mg/kg, daily) in our hospital’s infusion clinic. He received 20 doses in total, with substantial improvement (Figure 2). By the end of therapy, the lesion had flattened and regressed in diameter, with a residual irregularly shaped region of hypopigmented skin. The patient had 2 further recurrences on his left ear 3 and 11 months after his initial treatment. Each responded to foscarnet. Given the resistance to acyclovir and related compounds, no oral antiviral options were available for suppressive therapy. If the patient has additional recurrences, further management strategies will include immune modulation therapy with topical imiquimod.

<a href=”″ title=”Left forehead of an 80-year-old man with herpes simplex virus 2 infection after treatment with intravenous foscarnet, showing flattening and regression of the mass, with areas of postinflammatory hypopigmentation.” class=”highwire-fragment fragment-images colorbox-load” rel=”gallery-fragment-images-684742817″ data-figure-caption=”

Left forehead of an 80-year-old man with herpes simplex virus 2 infection after treatment with intravenous foscarnet, showing flattening and regression of the mass, with areas of postinflammatory hypopigmentation.

” data-icon-position data-hide-link-title=”0″>Figure 2:Figure 2:

Figure 2:

Left forehead of an 80-year-old man with herpes simplex virus 2 infection after treatment with intravenous foscarnet, showing flattening and regression of the mass, with areas of postinflammatory hypopigmentation.


Herpes simplex virus 1 and 2 belong to the Herpesviridae family of DNA viruses. Infection with HSV is common; estimated seroprevalences among adults in Ontario are 51.1% for HSV-1 and 9.1% for HSV-2.1 The 2 primary clinical manifestations are oral and genital infection. Classically, HSV-1 is associated with oral infection and HSV-2 with genital infection, but the reverse trend is occurring with greater frequency.2 As with all Herpesviridae, HSV-1 and HSV-2 have the capacity for latency and can reactivate intermittently after primary infection. Primary oral infection can be severe, characterized by painful gingivostomatitis and pharyngitis, with exudative, ulcerative lesions of the oropharynx. Recurrences tend to be mild and are characterized by painful vesicular lesions, classically located at the vermillion border. Similarly, primary genital infection is typically more severe, with bilateral, painful, ulcerative lesions, regional lymphadenopathy and systemic symptoms (such as fever, headache and malaise). Recurrent genital infection is usually less severe, with painful, unilateral, vesicular and ulcerative lesions. Other cutaneous manifestations include herpetic whitlow and herpes gladiatorum, the latter of which occurs in the setting of contact sports.3 Herpes simplex virus 1 and 2 can also cause infection at other sites, such as the anus and perianal skin, particularly among men who have sex with men (MSM).

Mucocutaneous HSV infections are typically diagnosed by HSV PCR of swabs obtained from herpetic lesions. Acyclovir and related compounds are first-line therapies (Table 1).4 Treatment is associated with reduced symptom duration and decreased risk of transmission, and should be started as soon as possible after symptom onset.4 Recurrent episodes are usually self-limited and antiviral therapy may not be required for patients with minimal or mild symptoms. For patients with frequent (i.e., episodes at least every 2 mo or at least 6 times/yr) or severe recurrences, daily suppressive antiviral therapy can be considered and should be re-evaluated annually.4

Table 1:

First-line treatment of genital herpes simplex virus infection*

Hypertrophic HSV infection is an atypical and uncommon manifestation of HSV. Described cases have most commonly involved the anogenital structures. In a review of 110 cases, 76.4% were anogenital; lesions of the oropharynx, nose, ears and ocular structures have also been reported.5 The clinical course is chronic and can be disfiguring, and the appearance is often mistaken for cutaneous malignant disease. Hypertrophic HSV infection has predominantly been described among people living with HIV infection. An association with immune reconstitution inflammatory syndrome has been hypothesized, although many cases have been described in patients on stable antiretroviral therapy with long-term virologic suppression.6 Anogenital involvement is most commonly seen among people living with HIV infection and may be related to sexual practices in MSM. Cases have also been seen with other forms of cellular immunodeficiency, such as hematologic malignancy, solid organ transplantation and congenital immune deficiencies (including common variable immunodeficiency secondary to T-cell lymphopenia, congenital T-cell deficiency syndrome and hyperimmunoglobulin E syndrome related to STAT3 sequence variations).5,6

The pathogenesis of hypertrophic HSV infection is poorly understood, although it may reflect chronic viral lytic replication in a host with underlying immune dysfunction.6 Our patient was taking ruxolitinib, a Janus kinase inhibitor, which is used for the treatment of myeloproliferative disorders including myelofibrosis. Increased frequency of Herpesviridae infections have been attributed to ruxolitinib, although these are most commonly varicella zoster virus infections rather than HSV.7 Diagnosis is generally made with biopsy of the lesion for histopathologic examination, HSV PCR or viral culture.5 Previous case reports have suggested that hypertrophic HSV infection is poorly responsive to conventional treatment with antiviral therapy.6 Alternate nonantiviral treatment modalities include surgical resection, topical imiquimod and thalidomide.5

Our patient’s management was complicated by resistance to acyclovir and related compounds via sequence variations in the UL23 thymidine kinase gene. Acyclovir and related compounds are the mainstay of treatment for HSV infections. They exert their effects through termination of viral DNA transcription.8 Upon entry into host cells, these antiviral agents undergo 3 consecutive phosphorylation reactions with conversion to acyclovir triphosphate, the active form.8 The first phosphorylation reaction is by viral thymidine kinase, while the second and third phosphorylation reactions are by host cell enzymes.8 Resistance to these compounds is primarily seen in immunocompromised hosts, such as people living with HIV infection and recipients of solid organ transplants.9 It is most often related to previous substantial exposure to acyclovir and related compounds.9 Our patient was immunocompromised owing to myelofibrosis and treatment with ruxolitinib, and had exposure to multiple courses of antiviral therapy over the previous 3 years, increasing his risk of resistance. Resistance mediated by sequence variations in the UL23 thymidine kinase gene results in absent, low production or altered activity of viral thymidine kinase, thereby preventing the first phosphorylation reaction. Less commonly, variations in the UL30 DNA polymerase gene result in target site alteration.8 In Canada, resistance genotyping is performed by Sanger sequencing at the National Microbiology Laboratory in Winnipeg.10 Alternate antiviral agents that can be used for resistant HSV include foscarnet and cidofovir; we prescribed the former for our patient. Foscarnet and cidofovir are inhibitors of viral DNA polymerase, but unlike acyclovir and related compounds, do not require phosphorylation by viral thymidine kinase. Both agents are administered intravenously and are associated with substantial risk of nephrotoxicity. Patients should be closely monitored for renal impairment and electrolyte disturbances; aggressive hydration and electrolyte replacement may be required.

We report a case of hypertrophic HSV infection in a man with myelofibrosis and substantial previous exposure to antiviral treatment, which was resistant to treatment with acyclovir and related compounds. Hypertrophic HSV infection is uncommon but can be seen in patients who are immunocompromised, most commonly people living with HIV infection. Resistance to antiviral agents should be suspected in patients who do not respond to conventional treatment, especially in patients who are immunocompromised or those with repeated antiviral exposure.

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


  • Competing interests: None declared.

  • This article has been peer reviewed.

  • The authors have obtained patient consent.

  • Contributors: Charlie Tan and Wayne Gold led the conception and design of the work. Charlie Tan wrote the first draft of the manuscript. All authors revised the manuscript critically for important intellectual content, approved the final version to be published and agree 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:



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Wellness and rejuvenation on a Whistler weekend



Reviews and recommendations are unbiased and products are independently selected. Postmedia may earn an affiliate commission from purchases made through links on this page.

The freshness of spring is giving way to the languor of summer. It’s also that time of year when I step up my health and fitness habits, with the help of a wellness weekend getaway. Check out these ten wholesome ways to experience Whistler.

1. Eat well, be well at a new event series

Nourish by Cornucopia
Savour local cuisine at Nourish by Cornucopia from June 2 to 30. Photo by Darby Magill

Making its debut the Nourish Spring Series by Cornucopia celebrates the season every weekend in June with farm-to-table fare, farm tours, lavish wellness dinners, healthy brunches and activities to refresh both mind and body. Sit down to a four-course spring harvest tasting menu (Brome Lake duck breast with Pemberton beets, anyone?), brush up on grilling skills with an expert chef, pick up painting pointers on an art picnic or jump into an outdoor Zumba class. Order tickets online at

2. Chill at a spa

Scandinave Spa
For wellness treatments it’s hard to beat Scandinave Spa. Photo by Chad Chomlack

With more than 12 spa facilities in town, it could be said that Whistler has everyone’s back. Pop into the Whistler Day Spa for a 75-minute stress relief massage using Swedish relaxation techniques or the Taman Sari Royal Heritage Spa for an 80-minute herbal steam massage using pouches filled with Javanese turmeric, ginger and other spices. Have more time? Dip into the hot-cold-and-relaxing thermal journey at the silent Scandinave Spa Whistler, home to open-air pools, cold-plunge baths, a Finnish sauna, Nordic showers and solariums in a tranquil forest setting.


3. Lace up for new guided hikes

Hiking in Whislter
Fresh mountain air and beautiful views are two reasons to go hiking. Mark Mackay Photo by Mark Mackay

Trek past alpine meadows flush with wildflowers on the way to glacier-fed Garibaldi Lake or meander through a fragrant rainforest before taking a dip in Crater Rim’s warm Loggers Lake. These are just a couple of guided hike options from Mountain Skills Academy & Adventures. Prefer to stay close to town? Sign up for the Whistler Alpine Hike and explore the gondola-accessed terrain of Whistler Blackcomb.

4. Embark on an ebike adventure

Valley Trail
Explore Whistler’s car-free Valley Trail, a 46-km network of paved paths and boardwalks. Photo by Justa Jeskova

Sneak in some good clean fun with an ebike rental or guided tour. Explore Whistler’s car-free Valley Trail, a 46-km network of paved paths and boardwalks linking the resort town’s neighbourhoods and lakes, beaches, parks and viewpoints along the way. Go it alone or hop on a full-suspension electric-assist mountain bike with Whistler Eco Tours for a two-hour guided ride. Prefer an old-school ride or want to hit the alpine trails? Comfort cruisers, cross-country and downhill bikes are also on hand.

5. Expand the mind at an Indigenous exhibit

The Squamish Lil’wat Cultural Centre
The Squamish Lil’wat Cultural Centre is a cultural connector. Photo by Justa Jeskova Photography

You have until October to view, the Squamish Lil’wat Cultural Centre’s Unceded: A Photographic Journey into Belonging. Shot at striking locales throughout the Sea to Sky Corridor, the exhibit brings together aspects of ancient traditions, modern Indigenous life, and colonization and development. Behold the bear dancer on Blackcomb Mountain, the cultural chief in the Fairmont Chateau Whistler lobby and the Squamish Nation chair standing in the middle of downtown Vancouver’s West Cordova St.

6. Get down, be healthy at a new café

Rockit Coffee
The new Rockit Coffee in Whistler Creekside boasts a retro theme. Photo by Leah Kathryn Photography

Boogie back in time to the ’70s and ’80s at the new Rockit Coffee in Whistler Creekside. From the speaker-lined wall and vintage phones, radios and ghetto blasters to menu items like Espresso Greatest Hits and Drinks Just Wanna Have Fun, the colourful café exudes a decidedly retro vibe. Pull up a chair and order a nutritious Aero-Smoothie – choose from the Green Day, Bananarama or Strawberry Fields Forever – and pair it with a Veggie Eilish breakfast wrap or Prosciutto Rhapsody sandwich.

7. Check into wellness

Fairmont Chateau Whistler
The Fairmont Chateau Whistler. Photo by Tal Vardi

Go for the Fairmont Chateau Whistler’s healthful options like daily yoga classes, guided excursions and access to pools, steam rooms, the fitness centre, tennis court and (soon) new pickle ball courts. But stay for the regionally sourced seasonal menus ­– complemented by the rooftop garden’s bounty from May to October – and no-proof cocktail selection in the Mallard Lounge.

8. Float down a winding river

River of Golden Dreams
Canoeing the River of Golden Dreams. Photo by Mike Crane

Canoe, kayak or stand-up paddleboard along the meandering five-km-long River of Golden Dreams. After putting in at Alta Lake, paddle past riverbanks lined with wildflowers, foliage and forest, all the while keeping an eye out for beavers, otters, eagles and bears. Newbie paddlers are advised to go with a guide, as changing water levels can make for tricky steering and mandatory portages.

9. Connect with nature on a new birding trail

BC Bird Trail
Watching for activity on the BC Bird Trail. Photo by Tourism Whistler

Watch for whiskey jacks, Clark’s nutcrackers and, come summer, lots and lots of swallows along the Sea to Sky Bird Trail. The fifth and most recent route to be added to the BC Bird Trail network along the Pacific Flyway, the new trail takes birders to alpine heights (lift ticket required) where they can spot olive-sided flycatchers and various raptors. Then it’s off to Rainbow Park on Alta Lake to spy common yellow throats and merlins.

10. Wake up beside a lake

NIta Lake lodge
NIta Lake lodge is steps to the lake. Photo by Nita Lake Lodge

Perched along the southern tip of Nita Lake in Whistler Creekside, Nita Lake Lodge checks off all the boxes for a dreamy wellness escape. Start with stunning water and valley views from luxe suites, currently undergoing a modern refresh slated to wrap in time for summer. Then there’s the new onsite restaurant, The Den, where plant-based alternatives share space with meat and seafood items on the seasonal menus. Topping off a salubrious stay at Whistler’s only lakeside hotel is an award-winning spa with rooftop hot tubs.



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HIV stigma index researchers look for Manitobans with positive diagnoses to share experience



Manitoba researchers looking for people to take part in a national HIV Stigma Index project are only about halfway to their goal of hearing from at least 75 people living with a positive diagnosis.

The international peer-driven research project helps understand the stigma associated with HIV and supports those living with a diagnosis.

“I wouldn’t say that anybody ran out and said ‘I’m gonna go get HIV today and see how that happens.’ Things happen to people and it’s our duty as human beings to support people no matter what they’re going through,” research co-ordinator Arthur Miller told CBC Information Radio Wednesday.

The Canadian HIV Stigma Index is a community-led and community-based research study, part of the international implementation of the People Living with HIV Stigma Index project


Participants are interviewed by another person living with a positive diagnosis. Interviews are about an hour-and-a-half long and can be done in person, by phone or through a video conferencing platform, said Miller, a Mi’kmaw HIV activist based out of Nova Scotia and research co-ordinator of the project with REACH Nexus, under the MAP Centre for Urban Health Solutions at Unity Health Toronto.

The national project has been done in Ontario, Quebec, Atlantic Canada and British Columbia, and this is the second time it’s being done in Manitoba, with an updated survey.

Researchers collect information related to stigma, discrimination and human rights, with the aim of better understanding the social determinants and stigma across systems like health care, schools and legal fields. The research aims to help people develop supports and policies at both local and national levels.

Peer-driven aspect crucial

Jared Star, a research manager at Winnipeg’s Nine Circles Community Health Centre, which specializes in HIV prevention and care, said the HIV Stigma Index’s peer-driven aspect is crucial for participants.

“They know that they won’t be judged,” he said. “They won’t have to explain situations and details that come naturally for them, because they’re talking to somebody with the same experience.”

Star is also a research consultant and PhD student with expertise in sexual health, alongside his work with Nine Circles, which is working closely with Miller on the project.

“It’s better for the study if we can collect the data in a shorter period of time, but because it’s qualitative research, it tends to take longer than a survey,” said Star. “But the more we can get up front and faster, the better.”

Jared Star is a research manager for Nine Circles Community Health in Winnipeg. (Submitted by Jared Star)

Star said the information gained from the project will help people move from a place of supporting and sustaining stigma to actively challenging and resisting it.

“I think if we do a good job and we’re able to get that information and then develop interventions that target stigma, we will be able to contribute to a reduction in HIV infections in Manitoba,” he said.

Education key to understanding 

Much more is known about HIV now than 30 years ago — like how to prevent transmission and that it’s no longer a death sentence.

With proper care, people who are HIV positive can lead long, healthy lives.

Miller said education is key and pointed to the fact that many don’t understand somebody with an undetectable viral load who adheres to treatment can’t transmit HIV through sexual intercourse.

“This is big for people with HIV,” he said. “For me, it felt like I got part of my life back.”

Manitobans willing to share their experiences through the HIV Stigma Index project can contact Miller at or by phone at 1-877-347-1175 to begin the process.

“The great thing about this study is we’re building this network of people living with HIV,” Miller said. “You’re going to be talking with someone living with HIV, so they can relate and share some experiences.”



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May 27, 2023 coronavirus update for Oakville



This is Oakville’s coronavirus update for Saturday, May 27, 2023. New, active cases of COVID-19 in Halton have nearly doubled for the second week in a row, and outbreaks at local long-term care homes are growing.

Oakville is reporting 22 new cases this week, about the same as the week before. But these last two reports from Halton regional health are the highest numbers of new cases in months – and active cases are now trending upwards by 50-100% weekly.

The outbreak that opened earlier this month at Oakville’s West Oak Village long-term care home has been contained to the Harbour floor. But there are two new outbreaks that have opened this week in other parts of Halton, including one at Oakville’s Northridge home on the Chisholm floor.

Halton continues to fall behind on our booster shots: only 1 of every 10 people in Halton have a full series of immunization, and the percentage of residents with outdated immunization has grown every week since the start of 2023. Among those 40 and under, those fully immunized is now below 5%.


The United States this week has said they and the CDC will no longer be tracking new, aggregate daily COVID-19 cases and deaths or new nationwide testing data.

The World Health Organization (WHO) has declared that after more than three years, the COVID-19 global health emergency is now over. WHO has determined that “COVID-19 is now an established and ongoing health issue which no longer constitutes a public health emergency of international concern (PHEIC).”

765 million cases of COVID-19 have now been recorded worldwide since the start of the pandemic; 6.9 million people have died.



**Vaccine booking: Fourth doses (second booster doses) of vaccine are now available for anyone in Halton age 5 and up, though fourth doses must be at least five months since your last dose and 90 days since having COVID-19.

Halton continues to book first and second-dose vaccinations for all residents age six months and older, plus third-dose boosters for anyone age 5 and up.

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