Recurrent Herpes Labialis

Recurrent Herpes Labialis
James Paterson, PhD Mona Kwong, MSc Pharm
Asessment and Non-prescription Treatment
This program has been approved for 1.5 CEUs by the Canadian Council on Continuing Education in Pharmacy CCCEP #268-0405 This lesson is valid until April 30, 2008
EP
This lesson has been sponsored with an unrestricted educational grant from
All material 2005 MediResource Inc.
Disclaimer
e have done our best to produce an accurate, timely, and educational Learning Series. However, MediResource Inc., the sponsors, the authors, the reviewers, and the editors assume no responsibility for any errors or consequences arising from the use of information contained within this program. With the constant changes in practice and regional differences, it remains the responsibility of the readers as professionals to interpret and apply this lessons information to their own practices. All rights reserved. For this lesson, in compliance with sections 10.2 and 10.3 of the Guidelines and Criteria for CCCEP Accreditation, the author, John Hawboldt, and MediResource Inc. report no real or potential conflict of interest in relation to the sponsor of the CE lesson. Tom Smiley has previously received an honorarium from the sponsor for speaking on an unrelated topic.
Learning objectives
he goals of this lesson are to describe cold sores and their treatment, with emphasis on their etiology and pathogenesis. This lesson also emphasizes the pharmacological actions and interactions, therapeutic applications, and implications of therapies available with an emphasis on non-prescription medications. It also provides information that can be used to counsel patients and a case study that helps focus therapy on prevention and treatment at the first indication of a cold sore. At the conclusion of this lesson, the reader should be able to: 1. describe the etiology, pathophysiology, and communicability of oral herpes simplex viral (HSV) infection, including primary infection, latency, and recurrence of the virus; 2. define cold sores and identify their cause; 3. characterize patient presentation of oral recurrent herpes labialis (RHL) including the stages of a recurrent episode; 4. be able to differentiate between and discuss methods for diagnosing oral RHL, canker sores, and other orofacial afflictions; 5. identify non-prescription and prescription therapies for treating oral RHL including their classification, mechanism of action, adverse effects, and place in therapy; 6. apply the concepts learned to counsel patients with oral RHL about current therapies with an emphasis on non-prescription treatment, and techniques designed to avoid recurrence, relieve symptoms, and prevent the spread of infection.
Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Authors
James Paterson, PhD James Paterson completed his PhD in tumour suppressor genes at the University of St. Andrews in Scotland. Dr. Paterson is currently a consultant with Scientific Insights Consulting Group Inc. where he works with healthcare companies to teach and explain evolving medical and scientific information in a variety of subject areas. Dr. Patersons expertise lie in oncology, respirology, and gastroenterology. During his career he has developed and delivered educational programs to undergraduates, post-graduate students, physicians, clinicians, and pharmacists. Dr. Paterson and his company work closely with clinicians/key opinion leaders in a number of subject areas and remain up to date with the literature to ensure that their information is accurate and within current treatment guidelines and/or advanced treatment regimens. Mona Kwong, MSc Pharm Mona Kwong is a pharmacy manager of Howe Street Pharmacy in downtown Vancouver. In her practice, Mona works with patients and other healthcare professionals to provide optimal pharmaceutical care. She regularly provides seminars to the general public about a variety of health- and pharmacy-related topics. She has also been involved in teaching pharmacy students by being a preceptor, by providing guest lectures, and by helping in the professional practice labs at the University of British Columbia. Mona acquired her scientific evaluation skills from obtaining her MSc (Pharm) from the University of British Columbia in 2002. She has co-written several peer-reviewed papers and numerous proceedings.
Expert reviewers
Tom Smiley B.Sc. Phm., Pharm.D. Tom Smiley is a pharmacist consultant who remains active in community practice with Dell Pharmacy in Brantford, Ontario. In addition to his clinical experience with patients over the past 25 years, Tom has written many CE lessons and workshops for pharmacists. These have included sun care, pain management, skin care, and atopic dermatitis lessons. Tom has also written patient brochures and disease management website postings on anti-infectives and antivirals in particular. Tom continues to develop and write workshops for pharmacists in the area of general pharmaceutical patient care concepts and disease state/medication management. John Hawboldt, BScPhm, PharmD Dr. Hawboldt is currently an Assistant Professor at the School of Pharmacy at Memorial University, and cross-appointed to the Health Care Corporation of St. Johns, Department of Pharmacy. He provides direct patient care to the Infectious Diseases Service. Dr. Hawboldt is also affiliated with the Drug Utilization Committee and the Antibiotic Utilization Committee of the Health Care Corporation and is responsible for drug utilization evaluations (DUEs), formulary reviews, and more. As a part of his teaching responsibilities, Dr. Hawboldt teaches the pharmacotherapy of infectious diseases and other therapeutic topics to final-year pharmacy students. Dr. Hawboldt is also on the School of Pharmacy Curriculum Committee that is looking at new and innovative ways to improve the pharmacy curriculum. Dr. Hawboldts interests include effective drug utilization, quality initiatives, and curriculum development. Current initiatives include a study on the effectiveness of surgical prophylaxis guidelines and medication reconcilliation, as well as the development of a clinical skills course in the school of pharmacy.

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Contents
1 1 3 4 5 5 6 6 7 7 7 9 10 10 11 11 12 12 12 12 13 13 14 1. Background 1.2 Biology Figure 1. Stages of a typical cold sore outbreak Table 1. Developmental stages of recurrent HSV-1 outbreaks 1.3 Distinguishing cold sores from other orofacial lesions Table 2. Factors known to activate recurrent herpes infections Table 3. Differentiating cold sores from canker sores Figure 2. Visual differences between cold sore and canker sore 2. Non-prescription treatments 2.1 Symptom support treatments Table 4. Examples of non-prescription products used for cold sores 2.2 Products with possible anti-viral activity 2.3 Viral entry blocking agents Figure 3. Proposed mechanism of action for docosanol 2.4 Unsafe or ineffective non-prescription remedies 3. Prescription treatments 4. Counselling patients 4.1 Goals of therapy 4.2 Role of the pharmacist 4.3 Patient information 4.4 Roles of other healthcare practitioners Table 5. Patient information on cold sores and their treatment Table 6. Patient information on treatment of cold sores with nonprescription products 14 Table 7. Situations where a medical practitioner should be involved in treatment and prevention of RHL 15 Figure 4. Pharmacist treatment algorithm for RHL 16 5. Conclusion 16 6. Case study 18 References 20 Questions

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1. Background
t is estimated that approximately 80% of all Americans are infected with the virus that causes cold sores.1 It is likely that Canadians are infected at similar rates; an Ontario study found 89% of individuals in their early forties were infected.2 Herpes Simplex Virus, Type 1 (HSV-1) is usually first caught in early childhood between 6 months and 14 years of age, typically before age 5. 70% or more of children show evidence of past infection by the time they reach age 14.3 Each year, more than one-third of the worlds population who harbour the causative virus suffer recurrent outbreaks of cold sores.4 The estimated 7 million-plus HSV-1infected Canadians have between 13 million and 20 million episodes of recurrent outbreaks each year. Of special interest to pharmacists is that 70% to 80% of cold sore outbreaks are treated with nonprescription products.5 While perhaps mild and inconsequential compared too many other viral infections, cold sores can be extremely physically uncomfortable. It may be painful to eat and talk. Cold sores have a tremendous negative stigma. These factors negatively impact the lives of not only the sufferers but those of family members and close acquaintances because of changes in routines to prevent spread of the virus.5 This article reviews contemporary knowledge about cold sores. It discusses their etiology and pathogenesis. This lesson explains the involvement of HSV-1 and describes means to manage its contagion with emphasis on self treatment with drugs that are available for attenuating symptoms. Pharmacists are an integral part of the healthcare team in terms of providing both product and counselling to aid patients to understand and comply with treatment. The designations cold sore and recurrent herpes labialis (RHL) will be used throughout this article to describe the lesion and the recurrent outbreaks of cold sores, respectively.
lesions are referred to as herpes genitalis. Although HSV-2 is transmitted sexually for the most part, it can be found in cold sore lesions due to oral-genital contact or by hand-to-mouth transfer.8 1.2.1 Primary infection The first encounter with HSV-1 is termed a primary infection. Primary infections are often subclinical and go unnoticed.9 Most primary infections are acquired during early childhood or adolescence through small breaks in the epithelium;10,11 HSV-1 is excluded from the body by an intact oral epithelium. The most frequent site of infection is through tiny cracks or fissures in the orofacial mucous membranes10 or damaged skin. The incubation period following inoculation is typically seven days. It replicates in epithelial cells causing lysis and local inflammation, resulting in formation of the vesicles characteristic of cold sore lesions. Affected individuals usually cannot recall when they experienced their first cold sore outbreak.5 Unlike other common viral infections, herpes viruses persist for the lifetime of the host they infect.5,11 1.2.2 Recurrent infection Recurrent HSV-1 lesions are common, approximately 20% to 40% of HSV-1 infected individuals will experience recurrent outbreaks after the primary oral infection.12 Once infection manifests as a primary attack, the virus ascends along peripheral sensory nerve fibers to the dorsal root ganglia of the trigeminal, facial, and/or vagus nerves. These ganglia are collections of nerve-cell nuclei located immediately outside the spinal cord. HSV-1 may remain latent in these ganglia and result in subsequent lesions throughout life.5 Latency is established after a brief period of virus replication. During latency, HSV-1 is not replicating and is able to hide from the host immune system. The infected individual will remain asymptomatic while the virus is in the latent stage. Currently available antiviral drugs that act by inhibiting viral DNA synthesis can neither prevent nor eradicate latency and are therefore ineffective on latent viruses.11 Within these ganglia, the virus remains inactive in its latent form until a protagonist trigger stimulates activation. Table 2 lists examples of triggers known to induce reactivation. The mechanism by which the virus is reactivated is not known.13 However, it is likely that cellular and host signals, in response to stress, reactivate the virus and it begins to replicate. The virus begins to replicate within the ganglion and simultaneously moves along the peripheral sensory nerves back to the skin where it continues to replicate in the epithelial cells. The prodrome symptoms, consisting of
1.2 Biology
Herpes simplex viruses are deoxyribonucleic acid (DNA) viruses of two antigenic types.6 HSV-1 is more frequently found at non-genital areas (i.e., above the waist). The normal site of involvement is at the orofacial sites. Lesions may also rarely occur elsewhere on the body. Humans are the only known host for HSV-1 3, most orofacial cold sores are caused by HSV-1.7 Another designation for the virus is herpes virus hominis. In contrast, herpes simplex virus, type 2 (HSV2) usually, but not exclusively, causes lesions in the genital area (i.e., below the waist). Resulting

tingling, itching, burning, tightness, swelling, or numbness, are caused by virus replication in the sensory nerve endings.3,5 The characteristics and symptoms of cold sore lesions result from viral replication, epithelial cell infection, and epithelial cell destruction because of the virus. Usually these lesions appear at the same sites as the primary infection or in other contiguous areas.5,10 Although reactivation may result in a recurrent outbreak, it may also result in the shedding of infectious virus from the skin or mucous membranes with no easily recognizable symptoms. The precise mechanisms underlying the process remain unknown. Similar to primary infection, the replication of the virus in the epithelial cells results in the formation of the external, visible cold sore. As the virus replicates and lyses epithelial cells, a vesicle forms that contains the released virus particles. The fluids that then fill the vesicle result from the immune reaction and the erythema that accompanies the virus replication. The dilation of the blood vessels allow for the accumulation of fluids and the migration of the immune cells to the vesicle. Ulcers form as a result of destruction of epithelial cells either through the lytic cycle of the virus itself or through the immune response destroying infected cells. The disease is characterized by unpredictable lesion recurrence. Some individuals may experience more than 12 outbreaks a year,4,14 although two to three outbreaks each year are typical.5 The frequency of recurrence varies greatly. 1.2.3 Cold sores Cold sores, the visible sign of recurrent HSV orofacial outbreaks, appear most frequently on the lips, at the juncture of the mucous membrane and the skin of the lips or inside the nose.3 They rarely occur inside the mouth unless the patient is immunocompromised. Herpetic lesions may also less frequently occur elsewhere on the skin (e.g., on the arm, finger, or leg).6 Cold sores are caused by inoculation with HSV-1.8 Infection may be asymptomatic, unnoticed, unrecognized, or present as symptomatic disease. Severity is highly variable both between patients and between outbreaks (that may occur irregularly) in a patient; as a result, there is no severity scale. Severity of an outbreak may vary from asymptomatic (i.e., release of active virus particles from the area normally affected by cold sore without the appearance of any of the symptoms associated with an outbreak) to large lesions that are slow to heal. Furthermore, two outbreaks may occur soon after one after another with long lesion-free periods before and after. In short, cold sores are highly unpredictable. In many cases, RHL presents little more than a nuisance.10
Symptoms Symptoms of the recurrent viral infection may include fever, headache, and muscle aches and pains as well as characteristic lesions. Malaise may also be present before lesions appear. This has led to the origin of the terms fever blister and cold sore.5 Fever and colds do not always precipitate an HSV-1 outbreak. The symptoms of fever or a cold may nevertheless be early systemic manifestations of HSV-1 reactivation that occur before skin lesions appear.5 The condition is also known as RHL or oral-labial herpes. The characteristics of HSV-1 and its role in the etiopathogenesis of cold sores are discussed in greater depth elsewhere in this article. Epidemiology The virus responsible for cold sores is extremely contagious and may be transmitted by intimate contact with an infected person. The virus may be acquired via saliva droplets through a kiss; from fomites such as eating utensils, drinking glasses or straws, razors, towels, cold sore medications, lip balms, and cosmetics; or airborne from a cough or sneeze. It is reported that as many as 10% of all infected adults release active HSV-1 particles in saliva periodically.3 Cold sores affect African-Americans and Caucasians equally.3 They occur frequently in individuals who live in crowded conditions and heavily populated areas as well as in persons of lower socioeconomic status. They are especially prevalent in areas of communal residence or socializing such as day-care centres or primary school classrooms,10 dormitories, prisons, and nursing homes. Persons present or residing in such surroundings who develop cold sore lesions should take special precautions to avoid contact with other people to prevent transmission of the virus. Persons with a cold sore should also avoid contact with anyone who has eczema, and anyone taking an immunosuppressant medication as these people are more susceptible to infection. 1.2.4 Stages of cold sore outbreaks Prodrome - Up to 60% of patients experience classical cold sore outbreaks that are preceded by prodromal symptoms (Table 1, stage 0), including pain, burning, itching, or tingling at the site where blisters will form. However, the prodrome stage is typically short (less than 24 hours). Prolonged prodromal symptoms are probably infrequent.15 The short prodrome phase is often missed or does not occur (in non-classical outbreaks) and patients may find cold sores unexpectedly, for example, when waking in the morning. Figure 1 graphically depicts the time line of a cold sore outbreak against

the relative clinical severity of each stage. About 25% of patients with prodromal symptoms have cold sore episodes that abort early. These individuals experience symptoms that do not continue beyond the erythema stage (Table 1, stage 1), after which symptoms resolve spontaneously. This resolution may result from a number of factors, including immune system destruction of virus, low replication rate of virus (due to weak trigger factors), early pharmacological intervention, or other factors affecting virus/host interaction. There is evidence that therapeutic intervention with antiviral medication early in the prodromal stage may abort some episodes that would likely lead to an otherwise classical syndrome.5 The prodromal stage is followed by erythema in 1 to 24 hours (Table 1, stage 1). Hours later, small yellow-white maculopapular ulcers on the vermilion border of the lip and extending to the adjacent skin appear (Table 1, stage 2). These quickly progress to small vesicles measuring 1 mm to 3 mm in diameter or large bullae (Table 1, stage 3).16 At first, they are filled with a clear, serous fluid and surrounded by a red halo. The margin of the lesion in the immediate vicinity appears swollen and red. The glands in the neck may become swollen, due to the bodys response to infection.7,8 The area around a cold sore feels firm due to local edema or swelling. It may appear reddened because of capillary dilation. Several vesicles may coalesce to form larger ones and persist for several hours before they break (Table 1, stage 4). At that time, they assume their characteristic yellowish and crusted appearance (Table 1, stage 5). The hard crust over mature lesions remains five to six days and is followed by a two- to three-day period during which overlaying skin may flake off (Table 1, stage 6). Edema and inflammation may continue throughout the event, making the lip look swollen and distorted. Cold sore vesicles should not be broken. The fluid they contain is laden with infective virus and can transmit infection to other areas. The period from rupture until the crusts are shed completely is the time of greatest risk for spread of infection. When vesicles rupture, the cold sore sufferer should take special care to minimize contamination of other parts of the body or other persons. Active virus remains present throughout the vesicle stage.10 HSV-1 lesions at orofacial sites may be life threatening to an immunocompromised patient, since there is a risk of the active virus disseminating to other tissues.11 Lesions are considered healed when the crust disappears and skin re-epithelialization is complete (Table 1, stage 7).5 Lesions that recur at the same site may lead to scarring. They may develop
quickly such that by the time a person first examines them, the first observation may be of vesicles. The lesion usually persists 7 to 10 days, but may continue for three to four weeks7; patients with lesions persisting for more than two weeks should seek medical consultation to ensure it is not a more serious condition. Pain may persist after the skin is healed. The clinical severity associated with each of the stages is presented graphically in Figure 1. The graphic depicts the clinical severity (a measure of symptom impact and contagion) of a possible outbreak. As outbreaks are highly variable, the length of different stages may vary as well as the duration of the entire outbreak, particularly when considering treatment. The stages of the outbreak are described in Table 1. Occasionally, a secondary bacterial infection occurs, especially if the lesions are large. The presence of pus under the crust of a cold sore suggests possible bacterial involvement. When bacterial infection occurs, appropriate treatment for the infection should be followed, typically in the form of topical antibiotics. If healing does not occur within two weeks, the individual should seek professional medical care. Persistent lesions may indicate the presence of a more serious affliction. Signs and symptoms of recurrent cold sore outbreaks are summarized in Table 1.
Figure 1. Stages of a typical cold sore outbreak
Adapted from Barbarash 2001.
1.2.5 Immunity Humans can develop partial immunity to HSV1. Most children are born with a level of passive immunity that corresponds with that of their mother. This immunity disappears by the end of the first few months of life. At that point, children are especially prone to development of cold sores. Around age 5, children begin to develop active immunity due to continued exposure to the virus. If the immune system is fully operational and

Table 1. Developmental stages of recurrent HSV-1 outbreaks

Stage Name 0 Prodrome Image When Day 1 Duration 1-24 hrs Description of stage Skin appears normal; tingling, burning, pain, or itching sensation is present; symptoms are felt to be a warning of the onset of the cold sore; virus can be cultured from skin Redness of the skin due to congestion and dilation of the capillaries
Erythema
Day 1-2
1-2 days
Papule/edema
Day 2
1-2 days
Small, solid, raised lesions with inflammation
Vesicle/pustule
Day 2-3
1-3 days
A blister-like skin elevation in which fluid is visible through the outer layer of the skin
Ulcer/soft crust
Day 3
1-3 days
Blister has collapsed or burst, forming a shallow gray ulcer or sore with bright red edge; floor of the ulcer may be moist; most painful stage; seeping fluid is highly infectious
Hard crust
Day 5-8
4-14 days Drying of the ulcer continues; ambercoloured crust develops into a hard dark scab
Re-epithelialization
Day 9-10
4-14 days Crust is lost; may be skin flaking, residual redness and inflammation, and distortion of lip; lesion is technically healed; skin irritation may persist. Complete disappearance of all signs of the disease
Normal skin
Day 10+
Adapted From 5

responsive, it will provide the individual with protection against HSV-1 by adulthood. Individuals who experience a primary herpes infection, especially during the early years of life, generally will suffer recurrences throughout life, although the incidence and severity of recurrent herpes outbreaks usually declines after the age of 35, the reason for this is unknown.3 1.2.6 Triggers of recurrent infection Cold sore sufferers should note the protagonist triggers presented in Table 2. These triggers can be divided into either internal or external stresses. An internal stress may not be easily controlled as a trigger as they affect the internal functions of the body, such as the immune system or hormonal systems. However, the external stresses affecting such things as the skin barrier are more preventable through lifestyle modifications or application of suitable protective agents. As a result, these factors should be identified and treated. Counteracting any and/or all of these triggers can greatly reduce symptoms from a recurring cold sore outbreak. For example, simple application of sunscreen or lip balm may prevent stress to the infected cells preventing an outbreak of RHL. Dry lips are more prone to outbreaks of cold sores. Patients should be advised to use a lip balm, applying it liberally. Furthermore, if an outbreak
happens, cold sores should be kept moist to discourage cracking of the skin. Cracks increase discomfort, increase the chance for secondary bacterial infections, and prolong healing time. Bland emollient creams serve this function. Products containing astringents should not be used for treating cold sores, since they promote drying and cracking. Ultraviolet B radiation is the most frequently cited stimulus for reactivation of HSV-1. Sunlight exposure is reported to precede the onset of recurrent cold sores in some people. Frequent application of a lip sunscreen product with SPF 15 value or greater to affected areas on the lips and face may help prevent outbreaks of cold sores.17 Wearing a wide-brim hat and avoiding sunlight as much as possible throughout the entire year can also help greatly to protect against ultraviolet B exposure with subsequent cold sore reactivation.
1.3 Distinguishing cold sores from other orofacial lesions
Table 2. Factors known to activate recurrent herpes infections 2,7,8,11

Internal (unpreventable) stress fever illness menstruation upset stomach or GI disturbance minor infections any disease that increases metabolism (e.g., diabetes, hyperthyroidism) presence of a second virus (e.g., common cold, flu) fatigue factors that depress the immune system External (preventable) stress windburn ultraviolet radiation (sunshine, tanning booths) chilling excitement emotional stress drying of the lips allergic reactions, including reactions to food any physical injury dental treatment
Ulcers as well as other lesions of the lips and inside the mouth appear fairly commonly throughout life. Some may appear in the morning without warning and are gone without a trace by evening. Not all orofacial lesions are cold sores. Some may occur from biting the lips or oral mucosa, or from irritation caused by ill-fitting dentures. Others may result from sensitivity or irritation to food, medication, tobacco products, or the use of hard toothbrushes. Many potentially serious pathologies can cause orofacial lesions. For example, they may signal an early symptom of fatal blood abnormalities such as agranulocytosis, or other morbid conditions such as erythema multiforme.10 A number of infective microorganisms such as the Coxsackie virus and the fungus Candida albicans may incite these lesions. In reality, it is not always possible or practical in a community pharmacy setting to accurately distinguish between cold sores and canker sores, or to differentiate these sores from more serious oral pathologies. If the symptom pattern matches either description presented in Table 3 and this corroborates positively with a patient history, there is strong indication that the condition is likely a cold or canker sore. At the same time, the presence of certain symptoms can confuse the issue further. Bad breath, for example, is characteristic of cold sores, but it can also signal that there is an accompanying bacterial or fungal infection. Patients should be referred to a doctor whenever a lesion around the lips or oral mucosa fails to heal within two weeks, appears to worsen in spite of self-treatment, or continues to bleed.

Table 3. Differentiating cold sores from canker sores

Cold sore Symptoms Pain Fever Halitosis Salivation Malaise Other Appearance
Canker sore Intense No No No difference No* No effect on neck glands Gray to grayish skin lesions surrounded by erythematous halos; usually 3 mm or more in diameter No (not viral)
Intense Yes Yes Increased Yes5 Swollen neck glands Yellow-white ulcer surrounded by a red halo usually 13 mm in diameter; gum margins swollen and red Yes (viral) 1014 days; healing without scarring
Contagious Duration
1014 days; healing without scarring
These symptoms may appear with these lesions, however, the absence of a symptom does not preclude the lesion of that type. Some symptoms are rare, such as fever, malaise, and swollen glands. *Malaise may be a symptom in severe conditions. Large lesions may leave scars.
Figure 2. Visual differences between cold sore and canker sore

Panel A shows typical cold sore with many small characteristic vesicles located primarily externally. Canker sores (Panel B) may occur singly or in small groups, have a larger round or ovoid ulcer (no blistering) and form primarily inside the mouth or on the tongue.
1.3.1 Canker sores Cold sores and canker sores share certain physical characteristics. These may confuse some patients into thinking the lesions represent the same affliction, and/or cause them to use inappropriate therapy in an attempt to control their symptoms. Distinguishing cold sores from canker sores is important because the two conditions have distinct etiologies, presentations, and outcomes. While some treatment modalities are similar, others differ greatly. The summary of distinguishing criteria provided in Table 3 may be helpful. Figure 2 shows both cold sore and canker sore.
Canker sores (aphthous ulcers, aphthous stomatitis) are annoying, painful, possibly familial, and recurrent lesions that appear on the inner lip, gums, inner cheek, soft palate, and tongue. They appear most commonly in the buccal and lip surfaces of the mouth. They vary in intensity from one person to another, and women are affected more often than men. Canker sores are not contagious and are probably caused by a bacterial infection (Streptococcus sanguis may be involved) rather than a virus. They are less serious than cold sores because of cold sore involvement with other conditions, such as erythema multiforme, and their highly contagious nature. Clinicians may misdiagnose the ulcerations of recurrent canker sores, which do not have an early vesicular phase like recurrent RHL, leading to inappropriate treatment.10 The initial symptom complex of canker sores usually consists of a localized burning or tingling sensation that leads to persistent and intense pain developing over the next 24 hours. By that time, an observable slightly concave and characteristically shallow, round, or ovoid ulcer from 3 mm to 15 mm or more in diameter can be seen. The sores have a slightly raised yellowish border surrounded by a bright red zone. Canker sores may appear singly or in groups. Two to three ulcers commonly occur together during each outbreak, but it is not unusual for 10 to 15 ulcers to develop in some persons. Over the course of a week, the lesions become encrusted with a yellowish opaque substance. Pain persists for several days, although a sensation of slight pressure or irritation often remains for a

few additional days. Canker sores normally heal without scarring. 1.3.2 Oral cancers Oral cancers normally appear initially as a visible mouth ulcer. Oral cancer is of special concern because its pathogenesis is poorly understood and patient prognosis is often guarded. Symptoms include mouth ulcers that do not heal, persistent bleeding of tissues in or around the mouth, and swelling of the palate and adjoining tissues as well as sensations of tingling, numbness, and pain. Such subjective symptoms can lead an individual to a common misconception that it is a cold sore or canker sore, rather than cancer, that is at fault.
2. Non-prescription treatments
Inappropriate treatment for an HSV-1 infection may be ineffective or could worsen the lesion (see section 2.4 for further discussion).10 Because of the pain, disfigurement, and psychosocial impact of RHL, patients with cold sores seek a safe and effective therapy.16 Although cold sore episodes are generally not serious and have a self-limited course, many people with the condition seek treatment, not only to relieve the discomfort and pain of the lesion but also because of personal concern about appearance and the possibility of transmis-
sion.4 However, others do not seek treatment because of a perception that treatments do not work or are not available.5 At present, most safe and effective non-prescription products to relieve cold sore symptoms contain topically applied skin protectants and/or external analgesics/anaesthetics. Formulations commonly include gels, creams, ointments, or lip balms that contain ingredients for palliation of symptoms but do not directly prevent viral infection, spread, or alter the course of the outbreak. Most products also include petrolatum or other bases to add moisture and form a protective barrier over the lesion. The presence of the barrier itself often improves the symptoms and aids healing. Table 4 is a representative sampling of non-prescription products available for the treatment of cold sores, including the ingredients and the possible effects of the product.
2.1 Symptom support treatments

2.1.1 Skin protectants Skin protectants provide a mechanical barrier to guard exposed skin surfaces from harmful or annoying stimuli. Safe and effective skin protectants include allantoin (absorbent); dimethicone (soothing, relieving irritation); cocoa butter, petrolatum, white petrolatum, and shark liver oil (emollient); and glycerin (absorbent, soothing,
Table 4. Examples of non-prescription products used for cold sores

The table shows the various products that may be found in a standard drug store, and is divided to reflect products that are found in the cold sore remedy section of the drug store as well as those that specifically state a use for cold sore treatment (i.e, lip conditioners and cold sore remedies, respectively). Note that inclusion in the cold sore remedy section does not imply any better efficacy for the relief of cold sore symptoms, but reflects the patients view of the cold sore remedy shelf. Product Lip conditioner Kank-A Liquid Blistex Lip Ointment
Manufacturer Blistex Inc. Local anaesthetic Blistex Inc. Local anaesthetic Blistex Inc. Local anaesthetic Carma Lab Franklin, WI
Ingredients Benzocaine 20%, cetylpyridinium chloride 0.1% Medicinal: allantoin 1%, camphor 0.5%, phenol 0.5% Medicinal: camphor 1%, menthol 1%, phenol 0.54% Mixture of occlusive emollients, emollients, and humectants. Also contains camphor, menthol, and phenol
Blistex Lip Medex
Carmex
Moisturizer; supports skin barrier; local anaesthetic

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Product Chapstick SPF15
Manufacturer Whitehall-Robins Inc.
Ingredients Medicinal: octyl methoxycinnamate 7.5%, oxybenzone 3.5% Nonmedicinal: mixture of occlusive emollients, emollients, and humectants Mixture of occlusive emollients, emollients, and humectants Mixture of occlusive emollients, emollients, and humectants Mixture of occlusive emollients, emollients, and humectants. Also contains camphor, menthol, and phenol Medicinal: octyl methoxycinnamate 7.5%, benzophenone-3 4.0% Nonmedicinal: mixture of occlusive emollients, emollients, and humectants
Sunscreen; moisturizer; supports skin barrier Labello Regular
Beiersdorf Canada Inc.
Moisturizer; supports skin barrier Labello Med
Beiersdorf Canada Inc.
Moisturizer; supports skin barrier Life Brand Cold Essentials
Norwood Packaging Ltd.
Moisturizer; supports skin barrier; local anaesthetic Neutrogena Lip Moisturizer SPF15
Johnson & Johnson
Sunscreen; moisturizer; supports skin barrier Cold sore remedy Abreva GSK Consumer Healthcare Medicinal: 10% docosanol Nonmedicinal: sucrose stearate, sucrose distearate, light mineral oil, propylene glycol, benzyl alcohol
Treatment of cold sores; shortening of pain/b urning; speeds healing; prevents spread of infection when used early Cold Sore Anbesol Whitehall-Robins Inc. Medicinal: benzocaine 20% Nonmedicinal: benzyl alcohol, carbomer, D&C Yellow No.10, FD&C Blue No.1, FD&C Red No.40, flavour, glycerin, methylparaben, polyethylene glycol, propylene glycol, saccharin Medicinal: heparin sodium 160 USP units, zinc sulfate 5 mg Nonmedicinal: carboxymethylcellulose, glycerin, methylparaben, polysorbate, propylparaben, water
Local anaesthetic Lipactin
Novartis Consumer Health Canada
Symptomatic treatment of cold sores; heparin may block virus adsorption; zinc may inactivate virus Viractin Gel Zilactin
Medibrands Inc. Local anaesthetic Zila Pharmaceuticals Inc.
Medicinal: 2% tetracaine hydrochloride Medicinal: benzyl alcohol 10% Nonmedicinal: boric acid, hydroxypropyl cellulose, propylene glycol, purified water, salicylic acid, SD alcohol 37, tannic acid
Local anaesthetic, exfoliant

and emollient). Their softening and moisturizing actions keep the lesions moist to prevent drying or fissuring. This in turn reduces the occurrence of secondary infection and offsets the delayed healing and discomfort caused by dry and cracked tissue in and around the cold sore. Labels of non-prescription products that contain skin protectants as their active ingredient(s) may state that the products soften crusts (scabs) associated with cold sores and fever blisters and relieve dryness and soften cold sores and fever blisters. 2.1.2 External analgesics/ anaesthetics Local analgesics and anaesthetics include benzocaine, dibucaine, dyclonine, lidocaine, tetracaine, benzyl alcohol, juniper tar, camphor, menthol, phenol, and resorcinol. They suppress cutaneous sensory receptors, therefore preventing or suppressing the transmission of pain sensation by the nerves to the brain. They are safe and effective for the temporary relief of pain and itching associated with cold sores when used appropriately.8,13
best giving an indication of the effect of zinc. Other more systematic studies that include blinding and placebo controls do not support the efficacy of zinc in treating RHL, but can not rule it out.24 Finally, many of the studies reporting on the efficacy of zinc are confounded by the presence of other active ingredients in the formulations tested (such as local analgesics or anaesthetics) which may have an effect on the course of the outbreak and the symptoms. The efficacy of zinc alone in the formulation cannot be determined. In conclusion, although the efficacy of zinc cannot be ruled out, the studies to date do not support an in vivo activity or efficacy of zinc salts in treating RHL. Safety The safety of topical zinc is well understood. At higher concentrations, zinc salts can have an irritating effect on the skin.21 However, at the concentrations typically used in topical formulations (approximately 0.5% w/w), this is not an issue. Furthermore, topically applied zinc does not accumulate in the cells, nor does it penetrate sufficiently to enter the bloodstream. The use of zinc may have detrimental effects on cold sores; the drying caused by zinc sulphate may result in fissuring and increased discomfort and increase the chance of a secondary bacterial infection of the lesion.25 2.2.2 Heparin Mechanism of action The addition of heparin to a solution containing active virus results in the competitive attachment of heparin to viral envelope glycoproteins which effectively blocks these sites from interacting with the cell surface heparin sulphate (HS) protein, preventing viral penetration.26 Heparin reduces the binding of the virus to the cellular target in the cell lines tested in the laboratory. However, there may be other binding sites that are available for other cell surface molecules that are not blocked by heparin and other cell surface factors may also participate in the binding of the virus to the cell.27 Virus particles that are devoid of the glycoprotein that is responsible for binding of cellular HS are still infective.26 There are also reported differences in the interaction of HSV-1 or HSV-2 and HS28 on the cell surface, suggesting that, depending on the type of infection experienced by the patient, there may be differences in the efficacy of heparin for the treatment of RHL. Furthermore, there are indications that different strains of virus may have different sensitivity to heparin.29 Heparin sensitivity also changes for different cell types, suggesting that HS from different sources may be more competitive in binding the virus.26
2.2 Products with possible anti-viral activity

2.2.1 Zinc Mechanism of action The precise mechanism of action of zinc salts against the herpes virus is unclear and somewhat controversial. It is possible that zinc specifically inhibits viral DNA polymerase at concentrations lower than comparable cellular enzymes,18 preferentially disrupting the viral DNA replication. Zinc is tightly regulated homeostatically,19 making it unlikely to accumulate in the cell at high concentrations. Therefore, accumulation of zinc in the cells at high enough concentrations to disrupt DNA polymerase is unlikely without damaging the cell. More recent work has found that the primary activity of zinc salts against the virus is extracellular.20 It is possible that zinc is binding to viral cellular attachment points (glycoproteins) preventing virus attachment to the cell.19 Efficacy Although zinc is effective at in vitro suppression of viral DNA polymerase in cell homogenates18 and inactivation of free virus particles,19 the data regarding efficacy of zinc in the treatment of RHL is poor, even if abundant. Zinc has been used extensively for the treatment of herpetic infections.Reviewed by 21 Reports support the use of zinc to prevent and treat RHL.22,23 However, the data is largely anecdotal, lacks any clear controls, and lacks clear methodology for the study of the effects of zinc. As such, it must be considered poor data, at

Efficacy There are no clinical trials available for heparin efficacy. As such, it is difficult to determine the efficacy of heparin in treating RHL. However, there are a number of in vitro experiments that have demonstrated the heparin does block the entry of virus into target cells.26-29 Safety Heparin does not cross the skin barrier, so that it does not have any effect systemically. As such, it is safe when used as a topical application. 2.2.3 Formulations Lipactin (160 USP units of heparin sodium and zinc sulfate 5 mg in a clear, colourless, odourless gel; zinc/heparin formulation) is a product that has been approved by Health Canada for the symptomatic treatment of cold sores. Company clinical data show shortened duration and faster time to healing when using this formulation compared to placebo when treatment commences early in the outbreak.30 However, the clinical trial is small (54 patients, 23 treated, 31 placebo) and a peerreviewed report of the trial is unavailable (internal company data).
Figure 3. Proposed mechanism of action for docosanol

Cells are infected by virus through a process that starts with viral attachment to the cell membrane through glycoprotein interactions (step A). The virus then penetrates the membrane through a fusion process to introduce viral DNA into the cell (step B). The viral DNA then replicates using the cellular machinery (step C), new virus particles are formed and are released after damaging or destroying the cell (step D). The new virus particles are then able to infect other cells. Docosanol works by modifying the cell membrane (lower cell). The virus is able to adhere to the cell using glycoprotein anchors, however, it is not capable of penetrating the cell to introduce viral DNA (red B). This interrupts the virus cycle, preventing the spread to infection to uninfected cells.
2.3 Viral entry blocking agents

2.3.1 Docosanol Mechanism of action Docosanol is a water-insoluble alcohol belonging to a family of long-chain aliphatic alcohols.31 It is inactive against viruses that lack a lipid envelope (e.g., poliovirus, adenovirus, reovirus), indicating that the antiviral action of docosanol is related to the entry process of lipid-enveloped viruses into cells (see Figure 3).12,31 In vitro experiments show that once it is in a cell, docosanol is converted to n-docosanoic acid in a time-dependent manner, the antiviral drug inhibits fusion between the plasma membrane and the HSV envelope, effectively blocking entry of the virus into the cell.32 The exact mechanism by which this block occurs is not fully understood, however, it appears to be a modification of the host cell membrane as the turnover rate of docosanol corresponds to the turnover rate of the membrane.32 In short, docosanol prevents viral replication by blocking migration of the virus into the cell. Because of this action, the drug is most effective if used early in the course of an outbreak before a large number of host cells are infected.12,33 Efficacy Docosanol inhibits a broad spectrum of enveloped viruses in vitro including all lipid-enveloped
viruses tested thus far. In addition to HSV-1 and HSV-2, these include cytomegaloviruses, varicellazoster virus, herpes virus types 6 and 7, respiratory syncytial virus, human immunodeficiency virus (HIV-1), and influenza virus type A.31 Docosanol is most effective, as with all treatments, when treatment is initiated at the prodromal stage, decreasing in efficacy as the lesion progresses through erythema, papule, and vesicle stages. Application of any cream or ointment to support the skin and provide symptomatic relief at later stages may aid in the healing of the lesion. There are clinical trials studying the effect of docosanol on the symptoms and healing of cold sore lesions. In a 737-patient, double-blind, multicentre, placebo-controlled, randomized trial, the time to healing of docosanol-treated patients was 18 hours less than placebo-treated patients (4.08 days vs. 4.8 days, p=0.008, from start of treatment to lesion resolution).34 Furthermore, treatment with docosanol significantly shortened the duration of pain, itching, tingling, or burning (symptoms shortened by a median of 13.4 hours), time to

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complete healing of classical lesions (median time of 1.6 hours earlier), and cessation of the ulcer/soft crust stage (shortened by 7.7 hours).34 Application of the drug early (in erythema or prodromal stages) resulted in a shorter healing time of approximately four days with docosanol compared to placebo in a small trial of 63 patients (6.8 days to 2.5 days, p=0.0001)12 although the magnitude of this shortening must be questioned with such a small trial. Overall, even though the clinical effects may appear modest, a 15% decrease in the duration of a cold sore (18 hours) may have a significant effect on patient perception of the course of the outbreak and their overall quality of life during the episode. Further, the 737-patient trial, even though reporting only a 1.6 hour difference in complete healing, noted that this time was much greater at the 25th and 75th percentiles, suggesting a more profound effect on the course of the outbreaks than suggested. Resistance Viral resistance to docosanol has not been reported. Neither docosanol nor its metabolites block viral synthesis and/or its replication directly. Therefore, development of resistance to docosanol is unlikely. Should viral resistance emerge, the effectiveness of currently available prescription antiviral drugs would be unaffected as they target different processes required in the virus replication cycle. Safety Docosanol has an in vitro half-life of approximately three hours. Systemic absorption is insignificant, with plasma levels below detectable limits. It has an excellent safety profile, as indicated by the results of extensive and comprehensive toxicology studies.33 It is non-toxic when used as directed.31 Adverse events were mild and infrequent in the clinical trials, primarily consisting of a stinging sensation when applied.12,34 Other application site reactions and headaches have an incidence similar to placebo. 2.3.2 Formulations AbrevaTM is a 10% cream formulation of docosanol. It has been approved by Health Canada as a cold sore treatment during acute episodes of recurrent orofacial herpes simplex in adults. This formulation has demonstrated clinical efficacy to speed healing, may limit the spread of cold sore infection when used early, and reduces the duration of pain, itching, burning, and tingling associated with the infection.33
2.4 Unsafe or ineffective non-prescription remedies
Over the years, it has been popular to treat cold sores with astringents such as tannic acid, zinc sulphate,25 and other agents such as ether and ethanol that deprive the virus of moisture. There is no scientific evidence that these substances are effective, and healthcare professionals no longer recommend them. In fact, they may even aggravate cold sore healing. For example, tannic acid precipitates a protein-tannate layer over cold sores to form a mechanical layer that encourages bacterial colonization underneath. Other drug product ingredients that are considered to be unsafe and/or ineffective and thus cannot be labelled for treating cold sores include antihistamines, hydrocortisone, and counterirritants in concentrations higher than those approved for use. Antihistamines are useful in alleviating itching and pain associated with certain topical afflictions, but there is no conclusive evidence of its effectiveness in healing cold sores. With respect to hydrocortisone, its current class labelling guidelines indicate that it is effective in relieving inflammation and itching of responsive dermatoses. Cold sores, like other viral infections, are not responsive to steroids. Counterirritants (e.g., camphor >3%, menthol >1%) are inappropriate for use in treating cold sore symptoms. Dietary supplements including Lactobacillus organisms (L. acidophilus, L. bulgaricus), L-lysine, citrus bioflavonoids, red marine algae, and pyridoxine have been recommended over the years to modify cold sore discomfort. While these and other modalities remain popular in the lay press and are often promoted by non-pharmacy outlets, controlled clinical investigations have failed to prove their effectiveness. Aromatherapy, yoga, and meditation have also been touted as effective treatment for cold sores, but again, none has been scientifically proven effective.5,8
3. Prescription treatments
There are a variety of different prescription treatments for RHL. These are briefly described below. However, as with the non-prescription treatments discussed, timing is crucial to significantly effect the course of an outbreak. The sooner the treatment occurs in the outbreak, the more effect the treatment will have. Optimally, the treatment should occur during the prodromal stage, before the appearance of the vesicles. As the vesicles appear very quickly (in the course of a few hours), the ability to get an appointment with a physician, obtain a prescription, have it filled, and start treatment

11
quickly is unlikely. As a result, many prescription products will ultimately be given to patients with complicated diseases (high frequency, side effects, or other medical issues) or as a prophylactic measure in situations where an outbreak is more likely (undergoing facial procedures, dental trauma). Acyclovir/valacyclovir Acyclovir is available as either a topical (ointment or cream) or an oral formulation. The drug has extremely low bioavailability (oral formulation) and low penetration into the target area (topical formulation); however, the topical cream formulation has improved penetration when combined with frequent application. Acyclovir cream has been approved in North America as a topical treatment for RHL (application four to six times per day). Valacyclovir is an orally delivered L-valine ester of acyclovir that provides improved bioavailability (three- to five-fold) over oral acyclovir. It is an oral prodrug of acyclovir and is rapidly metabolised into valine and acyclovir. It has been approved as a single-day, high-dose effective treatment of cold sores in people with recurrent HSV when taken at the earliest signs of RHL outbreak. Acyclovir is a synthetic guanosine analog that terminates DNA synthesis in infected cells. It has high specificity for infected cells because of a multistep activation process. Acyclovir is activated to its active form by phosphorylation within the infected cell by viral thymidine kinase, followed by phosphorylation by cellular enzymes to an active triphosphate form that competes with deoxyguanine for incorporation into the proviral DNA strand. Incorporation of activated acyclovir into the strand prevents further elongation of the strand. The requirement of viral thymidine kinase for activation confers its selectivity for infected cells.Reviewed in 5 Penciclovir/famciclovir Similar to acyclovir, penciclovir is also a guanine derivative and also requires viral thymidine kinase and cellular enzymes to complete the activation of its antiviral activity. However, rather than terminating the synthesis of nascent DNA chains during DNA synthesis, it slows the synthesis of the virus but does not stop it. However, penciclovir has a higher phosphorylation rate with a longer cellular half-life than acyclovir. Similar to acyclovir, it also has poor bioavailability.Reviewed in 5 There is an approved prescription topical cream for herpes labialis available in the U.S. Famciclovir is a chemically modified form of penciclovir that is delivered orally and readily absorbed in the gastrointestinal tract and is rapidly converted to penciclovir. It is available in Canada and is indicated for the treatment of cold sores in immunocompromised patients.
4. Counselling patients
4.1 Goals of therapy
The goals of therapy are to alleviate discomfort, prevent secondary bacterial infection, and prevent auto inoculation of HSV-1 or its spread to other persons.8 Healing the lesions quickly is a more definitive goal.
4.2 Role of the pharmacist
Cold sores are afflictions that pharmacists are often called upon to confirm diagnosis and then suggest treatment. The reality of physicians attitudes towards supervising the treatment of milder cold sore conditions forms part of the necessity of pharmacists expertise. Moreover, historically there have been few effective treatments. Therefore, only a few patients seek professional medical care for relief of symptoms of cold sores.5 Pharmacists serve the primary healthcare needs of most people. This includes supplying non-prescription products that, in their best judgement, provide safe and effective treatment for a broad variety of afflictions. Patients need up-to-date, accurate information in order to make an informed choice to either self-treat their condition with nonprescription products or seek professional medical consultation and prescription antiviral products. The points provided in Tables 5 and 6 may be used to aid patients in their self-treatment of cold sores.
4.3 Patient information
Information and advertising of non-prescription products may be confusing to the patient. Although there are a number of authoritatively stated claims for a variety of products, including nutritionals, herbals, alternative therapies and other remedies, it is important to realize that most have not been scientifically tested for effectiveness in controlled trials. There are no guarantees that these products will aid in the resolution of a cold sore, and it is possible they may worsen some of the symptoms if they are not properly used. It is then important for healthcare professionals to recommend products that have evidence of efficacy and remember that most products may only provide some symptomatic relief, but not shorten the duration of cold sores. Additionally, some of these products can be expensive when compared to agents with proven efficacy and safety. Using unproven therapies may prolong the time to acquire relief compared to using an appropriate product recommended by a pharmacist, physician, or dentist. The diagnosis of cold sores is usually confirmed on the basis of clinical appearance and patient

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Table 5. Patient information on cold sores and their treatment

Cold sores are also called fever blisters and herpes outbreaks. Cold sores are not the same as canker sores. Do not squeeze, pinch, bite, or pick at blisters. If you notice yellow pus around your cold sore, you may have a bacterial infection. Coat the lesion with a triple-antibiotic ointment. See your doctor if the infection persists. Avoid eating acidic foods such as citrus fruits, tomatoes, pickles, or other foods such as salty snacks if they irritate your cold sore. Rinse your mouth as often as necessary with a commercial mouthwash product or a solution made by mixing one teaspoonful of salt in 500 mL of water. These remedies will help soothe cold sores and reduce irritation. Cold sores are contagious. Avoid contact with other persons during the period when the blisters are developing. Try not to touch your eyes or genital area unless you have first washed your hands thoroughly. Avoid oral sex during an episode as this can transmit the infection to the genitals. Gently wash the lesion area with a mild soap-free liquid cleanser and pat dry with paper towels. Discard used towels. Wash your hands carefully with a liquid cleanser and water and keep them away from cold sore lesions as much as possible. You may take analgesics such as ASA, acetaminophen, or ibuprofen to help relieve the severe pain of cold sores. Be sure to follow the directions for use. Children should not take ASA. Keep cold sore lesions moist to prevent drying and fissuring. Use a sunscreen of SPF 15 or greater on your lips and over the area of your face where cold sore blisters develop. Dont touch reusable applicators (lipsticks, lip balms, etc) directly to the cold sore; apply with a finger or other applicator and wash or discard immediately, as appropriate. Despite all caution, remember that it is possible to transmit herpes virus even when no blisters are present. history. Misdiagnosis can result in ineffective or inappropriate treatment, thereby worsening the lesion.10 Relief of symptoms of both cold sores and canker sores is possible with some of the same nonprescription products that contain skin protectants and/or external analgesics/anaesthetics. Because the two afflictions have separate etiologies and characteristics, their specific treatment differs. Pharmacists can use the information in Table 3 to
help differentiate between the two conditions to determine proper therapy. It is important to begin treatment as soon as possible after the first signs of a cold sore outbreak. Lesions evolve rapidly, with maximum severity often occurring within eight hours of initial symptoms. As a result, the effective therapeutic window is very small and it is essential that antiviral therapies be administered early.12,35-38 Any delays could reduce the benefit of the treatment to the patient. If the severity or frequency of outbreak necessitate, however, a referral to a physician is generally required. Most individuals are probably unaware that a virus causes cold sores. Patients presenting with cold sores should therefore be advised to avoid physical contact with others (e.g., kissing when lesions are present) and to use high standards of hygiene. Individuals without cold sores should refrain from contact with infected persons and from touching articles these individuals have used. Cold sores are self-limiting and usually heal within two weeks. If they worsen with selftherapy, persist beyond two weeks, or continue to occur, medical or dental consultation should be obtained. Cold sores should never be ignored. Furthermore, patients having excessive recurrence (e.g., more than six to eight recurrences per year) who are particularly sensitive to visible lesions, who have a history of other serious complications (such as erythema multiforme), or who are immunocompromised (because of transplant medication, or other diseases such as AIDS) may be suitable for suppression therapy using prescription (often oral) anti-viral drugs. They should be encouraged to consult their physician.
4.4 Roles of other healthcare practitioners

4.4.1 Medical doctors/general practitioners Patients do not often visit a doctor for RHL outbreaks for a number of reasons: a lack of personal time, frequent delays between obtaining an appointment and seeing the doctor (resulting in self-resolution of the outbreak), a belief by patients that the infection, although inconvenient, is not life threatening and thus not worth a medical visit, and/or a perception that effective treatments are not available.39 This last point may be partly true; when factoring the time required to see a doctor, to obtain and fill a prescription, and to begin treatment, the optimal treatment window may have passed with the medication having little effect on the course of the outbreak. However, there are a number of situations when a medical practitioner can and should be involved in treatment or prevention of RHL, as detailed in Table 7.

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Table 6. Patient information on treatment of cold sores with non-prescription products

Skin protectants and/or external analgesics/ anaesthetics This product is for the temporary relief of pain due to recurring cold sores when the condition has been diagnosed previously by a doctor, dentist, or pharmacist. Apply a thin layer of the product on your lesion before eating. This will ease the pain and facilitate chewing and swallowing. Apply the product directly to the lesion. Do not spread it over adjacent, non-involved areas. Cold sores may persist for 10-14 days. Drug products containing skin protectants or external analgesic ingredients will make the area feel comfortable, but will not shorten the duration of the lesions, cure them, or prevent their recurrence. Do not use this product continuously for a period longer than seven days unless on the advice of, and under the supervision of, a doctor or dentist. If irritation persists beyond 14 days, if inflammation develops, or if fever and infection develop, discontinue the use of this product and and immediately see a doctor. Keep this and all medications out of the reach of children. Do not use this product on children under 12 years of age unless on the advice of, and under the supervision of, a doctor or dentist. If you have diabetes and regularly suffer from cold sores, talk to your doctor. Self-treatment with nonprescription products may be restricted for you. Viral entry blocking agent (currently only docosanol) Early treatment will aid in resolving a cold sore sooner. Apply it to the affected area at the very first sign or symptom that a cold sore is going to appear. Remove all cosmetics from the affected area before applying this product; cosmetics can be reapplied over the medicine. Apply a thin layer of cream to completely cover the cold sore. A thin layer is all that is necessary. Apply this medicine five times a day until the sore is completely healed or as directed by your doctor, dentist, or pharmacist. This product may be used in children 12 years and older. There are a number of factors that are known triggers of cold sores, as discussed in this document. There are also a number of medical or dermatological procedures that may also trigger outbreaks of RHL. A patient with a history of RHL may be prescribed a treatment by their doctor
Table 7. Situations where a medical practitioner should be involved in treatment and prevention of RHL
For treatment pregnancy diabetics immunocompromised/immunosuppressed people children (under 12) pregnancy diabetics immunocompromised/immunosuppressed people more than 3 outbreaks per year dental surgery patients patients scheduled for dermatological procedures (peels, etc)
For prevention
before a planned procedure if there is a higher chance that the procedure will cause an outbreak. The treatment would not be necessarily used preventatively, but would be taken if an outbreak occurs. There are also other patients who may qualify for suppressive or preventative treatments, such as for those who find cold sores cosmetically uncomfortable, have excessive frequency of outbreaks, or have other medical conditions that would be complicated by outbreaks (such as immunosuppressed patients). Again, these patients would require the appropriate suppressive or preventative treatments prescribed under the direction of a doctor. Doctors may prescribe an ongoing treatment, or a treatment that is to be used if and when an outbreak occurs. For example, a patient with frequent outbreaks may be prescribed a single course of valacyclovir (one-day treatment) when there is no evidence of an outbreak to be used at the first signs of an outbreak, thereby shortening the time to obtain treatment. Patients should be encouraged to discuss their RHL with their doctors. This will ensure appropriate preventative, suppressive, or pre-prescribed treatments are available to the patient when required. 4.4.2 Dentists Dentists are often confronted by RHL because of the traumas that even routine dental care can inflict. As a result, they are often a primary resource to the patient with RHL. However, dentists are traditionally less likely to prescribe medications for non-dental complaints and may refer a patient to a pharmacist or a general practitioner.40 However, patients should be encouraged to discuss

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Figure 4. Pharmacist treatment algorithm for RHL

After initial diagnosis based on history of patient and specific symptoms to exclude other causes of the sores, counselling and patient education form a central part of treatment. Counselling about early treatment is critical because often, by the time the patient presents, it is difficult to have a significant effect on the length of the outbreak, although symptomatic treatment is important.
Patient with suspected HSL Patient with suspected HSL
Does the patient have exclusions to selftreatment? (e.g. immunocomprimsed/ suppressed, erthyma multiforme)
Yes
Refer to physician
No
Are the appearance and location of the lesions typical of canker sores?
Yes
Self-care of canker sores
No
Are the appearance and location of the lesions typical of RHL?
No
Refer to physician
Yes
Have the lesions been present longer than 14 days?
Yes
Refer to physician
No
Counsel on: Immediate lesion: Prevention of transmission Use of appropriate therapy to reduce symptoms and speed healing Continued use of skin protectant to keep lesions moist Use of topical antibiotic if lesions have secondary bacterial infection Triggers: Discuss potential triggers and avoidance techniques Advise use of sunscreen at all times Recurrent episode: Importance of treatment at first sign or symptom of recurrence
Are lesions healed after 14 days?
No
Refer to physician
Yes
Advise stopping therapy; avoid stress and triggers

15
any history of RHL with their dentist to ensure that proper prophylaxis is undertaken when the patient is undergoing procedures that are likely to cause an RHL outbreak (i.e., those that cause trauma to mouth and gums such as scaling and extractions, or those that stretch the lips excessively).
5. Conclusion
Each year, more than 50 million Americans and almost 7 million Canadian adults will develop symptomatic RHL episodes, characterized as a common and self-limiting infection with the formation of a blister or sore on the upper or lower lip.1,4,17 For many patients, cold sores cause considerable discomfort and psychosocial stress. Many patients simply do not seek treatment because they feel that therapy is limited and there is nothing available to them but to let the infection run its course. Given the variety of non-prescription symptomatic products available for cold sore treatment, the support and education provided by pharmacists to make informed decisions regarding the choice of therapy is essential to patients. There are many unproven claims for herbal or natural remedies. Few have been tested for clinical and adverse effects and they can be relatively expensive compared to agents with proven efficacy. Palliative support of symptoms may help to shorten the duration of these symptoms. A product with virallimiting activity is also available. Lastly, pharmacists play an important role in counselling patients with RHL about its prevention, transmission, and treatment. Efforts to provide pharmaceutical care and patient counselling can greatly improve patient outcomes. The pharmacist plays a central role in the treatment of RHL patients, often providing primary diagnosis and referral to other members of the healthcare team, as appropriate, or providing the most effective treatment for the patient. The pharmacist is also often more aware of other medical options than patients are and may recommend these to patients thereby providing improved quality of life.
having had to go to see the doctor twice in the past few months for first a throat and then an ear infection. He is an extremely busy individual. Hugh is 32, unmarried but dates socially, and works in an advertising firm. You remember that he is very concerned about his appearance. He wonders if you could help him out. He is booked up with meetings and just wants to get rid of it, whatever it is. Before advising Hugh on how to manage his cold sore - not canker sore - you should do a quick patient history to see if there are any contributing factors causing the problem so that you can counsel him on prevention as well as management. Recall that there are external and internal stresses known to activate recurrent herpes infection. External stresses are preventable and include windburn, ultraviolet radiation, chilly conditions, excitement, emotional stress, drying of the lips, allergic reactions to such things as food, physical injury, or dental treatments. Internal stresses are unpreventable and include fever, illness, upset stomach, minor infections, other viruses such as from colds, and fatigue. You determine the following profile: History Age 32 Currently presents with erythema at the corner of his lips. It was tingling the day before but he thought the skin was just dry from spending some time out in the sun doing his twice- weekly run. He has been licking his lips and applying facial cream to try to help moisturize the area.You question him about his previous cankers. He has had corner lip blisters in his last outbreak. He remembers that his corner lip area was red before he got the blisters. Hugh said it did not look good, especially since he has to work with so many people. He gets them about once or twice a year. Medication history none currently he has not tried anything in the past for cold sores Other information He has been working with a lot of people on projects lately to meet deadlines. They have been ordering in a lot of take-out meals for their office sessions.He has been drinking about five cups of coffee a day.He has also been tired because, in addition to his busy work schedule, he has been going out socially on a few dates during the last few months.
6. Case study
Its started again! I think I am starting to get another canker! I had one just a few months ago. I dont get it, its not like its cold out there or anything! exclaims Hugh Allan while rubbing at the red corner of his lips. You recall Hugh because he is very vocal individual. In his last visit, he picked up antibiotics and he was complaining about

16
External (preventable) stress exposure to ultraviolet radiation and potential windburn while running drying of the lip (he has not been drinking enough water during the day and has been drinking a lot of coffee) Internal (unpreventable) stress fatigue from work and social life What would you recommend? Because of Hughs previous history of cold sores and because he has factors that aggravate cold sores, you determine that he can be treated with a non-prescription product. You tell him because he has come into the pharmacy during the very initial stages of a cold sore, a non-prescription product may help him. Cold sore lesions will develop but a non-prescription product can shorten healing time. You recommend 10% docosanol which has been approved to be used in treating acute episodes of recurrent cold sores. You counsel him on the following points: Cold sores are not the same as canker sores. They are also known as fever blisters as sometimes fever occurs. Cold sores are a result of a herpes (viral) outbreak whereas canker sores are usually caused by bacteria. Cold sores are contagious. He should avoid physical contact with others and use high standards of hygiene while he is in a social situation. This includes avoiding kissing when lesions are present and ensuring that non-infected individuals avoid touching articles that he has used. This includes sharing eating utensils, drinking glasses, or straws. He particularly has to be careful since he has been working in close proximity with his co-workers and sharing take-out food. Cold sore areas should be gently washed with a mild soap-free liquid cleanser and patted dry with paper towels. Used towels should be discarded. Hands should be carefully washed with a liquid cleanser and water and kept away from cold sore lesions as much as possible. Blisters should not be squeezed, pinched, and picked at if they occur. Docosanol should be applied five times daily in a thin layer and should cover the sore. No facial cream should be applied on the area before
applying docosanol. The cold sore should heal within 10 to 14 days. The earlier the treatment, the earlier the cold sore will resolve. If yellow pus does occur around the cold sore, this may indicate a bacterial infection and he should see the doctor. He should also see the doctor if the cold sore persists for more than two weeks. Acidic foods such as citrus fruits, tomatoes, pickles, or other foods such as salty snacks should be avoided if they irritate the cold sore. Rinse the mouth as often as necessary with a commercial mouthwash product or a solution made by mixing one teaspoonful of salt with 500 mL of water. This may help soothe cold sores and reduce irritation. Taking an analgesic such as acetaminophen or ibuprofen will help relieve pain if it occurs. Applying a skin protectant or an external analgesic lip balm to the cold lesion especially before eating may help ease the pain and facilitate chewing and swallowing. Remind him that non-prescription drugs can work effectively in shortening cold sore healing time the sooner an outbreak is identified and treated. An outbreak can be non-symptomatic but there are certain symptoms that indicate an outbreak is coming. He may feel that same tingling he felt before this cold sore. There could also be burning, pain, or an itchy sensation at the beginning or he may have redness at the cold sore site like he has now. Since he runs outside, he would benefit from using a sunscreen of SPF 15 or greater on his lips where cold sore blisters develop. This reduces the chance of infection and helps in the discomfort caused by dryness around the cold sore. Tell him to decrease licking the lip area; it will also help to stay more hydrated due to his running and high coffee consumption. He should try to prevent outbreaks by keeping an eye on preventable external stresses. He should keep track of the frequency of his cold sore outbreaks, and, if it is excessive, he should talk to his doctor to assess the need for preventative treatment.

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References
1. Higgins CR, Schofield JK, Tatnall FM, Leigh IM. Natural history, management and complications of herpes labialis. J Med Virol 1993;Suppl 1:22-6. 2. Howard M, Sellors JW, Jang D, Robinson NJ, Fearon M, Kaczorowski J et al. Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 in men and women in Ontario, Canada. J Clin Microbiol 2003;41:84-9. 3. Pray WS. Non-prescription product therapeutics. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 53-74. 4. Boon R, Goodman JJ, Martinez J, Marks GL, Gamble M, Welch C. Penciclovir cream for the treatment of sunlight-induced herpes simplex labialis: a randomized, double-blind, placebo-controlled trial. Penciclovir Cream Herpes Labialis Study Group. Clin Ther 2000;22:76-90. 5. Barbarash RA. Update on treatments for Oral Herpes Simplex viral infections. Todays Therapeutic Trends 2001;19:39-58. 6. Magnussen CR. Skin and soft-tissue infections. In: Reese RE, Betts RF, editors. A practical approach to infectious disease. Boston: Little, Brown and Company; 1996. p. 104-6. 7. Cotran RS, Kumar V, Collins T. Robbins pathologic basis of disease. Philadelphia: W.B. Saunders; 1999. p. 759. 8. Flynn AA. Oral pain and discomfort. In: Allen LV, editor. Handbook of non-prescription drugs. Washington: American Pharmaceutical Association; 2000. p. 589-609. 9. Flynn AA. Oral health. In: Covington TR, editor. Handbook of non-prescription drugs. Washington: American Pharmaceutical Association; 1996. p. 50735. 10. Raborn GW, Grace M. Herpes simplex type 1 orofacial lesions. Herpes 1999;6:8-11. 11. Genital and orofacial herpes simplex virus infections - clincal implications of latency. Sandstrom, E. and Whitley, R. J. 1995. 1995. 12. Habbema L, De Boulle K, Roders GA, Katz DH. nDocosanol 10% cream in the treatment of recurrent herpes labialis: a randomized, double-blind, placebocontrolled study. Acta Derm Venereol 1996;76:479-81. 13. Colgin MA, Smith RL, Wilcox CL. Inducible cyclic AMP early repressor produces reactivation of latent herpes simplex virus type 1 in neurons in vitro. J Virol 2001;75:2912-20. 14. Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA 1997;277:1374-9.
15. Spruance SL, Wenerstrom G. Pathogenesis of recurrent herpes simplex labialis. IV. Maturation of lesions within 8 hours after onset and implications for antiviral treatment. Oral Surg Oral Med Oral Pathol 1984;58:667-71. 16. Khalifa MA, Lack EE. Herpes simplex virus infection. In: Conner DH, Chandler FW, Manz HJ, editors. Pathology of infectious diseases. Stamford: Appleton & Lange; 1997. p. 147-52. 17. Rooney JF, Bryson Y, Mannix ML, Dillon M, Wohlenberg CR, Banks S et al. Prevention of ultravioletlight-induced herpes labialis by sunscreen. Lancet 1991;338:1419-22. 18. Fridlender B, Chejanovsky N, Becker Y. Selective inhibition of herpes simplex virus type 1 DNA polymerase by zinc ions. Virology 1978;84:551-4. 19. Kumel G, Schrader S, Zentgraf H, Daus H, Brendel M. The mechanism of the antiherpetic activity of zinc sulphate. J Gen Virol 1990;71 ( Pt 12):2989-97. 20. Meshitsuka S, Ishizawa M, Nose T. Uptake and toxic effects of heavy metal ions: interactions among cadmium, copper and zinc in cultured cells. Experientia 1987;43:151-6. 21. Eby GA, Halcomb WW. Use of topical zinc to prevent recurrent herpes simplex infection: review of literature and suggested protocols. Med Hypotheses 1985;17:157-65. 22. Brody I. Topical treatment of recurrent herpes simplex and post-herpetic erythema multiforme with low concentrations of zinc sulphate solution. Br J Dermatol 1981;104:191-4. 23. Finnerty EF. Topical zinc in the treatment of herpes simplex. Cutis 1986;37:130-1. 24. Graham RM, James MP, Bennett S. Low concentration zinc sulphate solution in the management of recurrent herpes simplex infection. Br J Dermatol 1985;112:123-4. 25. MacCara ME. Cold Sores (Herpes Labialis). In: Repchinsky C, LeBlanc C, editors. Patient Self-Care. Ottawa: Canadian Pharmacists Association; 2002. p. 786-92. 26. Immergluck LC, Domowicz MS, Schwartz NB, Herold BC. Viral and cellular requirements for entry of herpes simplex virus type 1 into primary neuronal cells. J Gen Virol 1998;79 (Pt 3):549-59. 27. Mardberg K, Trybala E, Tufaro F, Bergstrom T. Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfateexpressing gro2C cells. J Gen Virol 2002;83:291-300. 28. Trybala E, Liljeqvist JA, Svennerholm B, Bergstrom T. Herpes simplex virus types 1 and 2 differ in their interaction with heparin sulfate. J Virol 2000;74:910614. 29. Trybala E, Roth A, Johansson M, Liljeqvist JA, Rekabdar E, Larm O et al. Glycosaminoglycan-binding ability is a feature of wild-type strains of herpes simplex virus type 1. Virology 2002;302:413-9.

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30. Novartis Consumer Health Canada Inc. Product Monograph: Lipactin Gel (Heparin sodium - Zinc Sulfate). 1988. 31. Marcelletti JF, Lusso P, Katz DH. n-Docosanol inhibits in vitro replication of HIV and other retroviruses. AIDS Res Hum Retroviruses 1996;12:71-4. 32. Pope LE, Marcelletti JF, Katz LR, Lin JY, Katz DH, Parish ML et al. The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process. Antiviral Res 1998;40:85-94. 33. GlaxoSmithKline Consumer Healthcare Inc. Abreva 10% cream product monograph. 2002. 34. Sacks SL, Thisted RA, Jones TM, Barbarash RA, Mikolich DJ, Ruoff GE et al. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial. J Am Acad Dermatol 2001;45:222-30. 35. Spruance SL, Overall JC, Jr., Kern ER, Krueger GG, Pliam V, Miller W. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med 1977;297:69-75. 36. Van Vloten WA, Swart RN, Pot F. Topical acyclovir therapy in patients with recurrent orofacial herpes simplex infections. J Antimicrob Chemother 1983;12 Suppl B:89-93. 37. Spruance SL, Freeman DJ, Stewart JC, McKeough MB, Wenerstrom LG, Krueger GG et al. The natural history of ultraviolet radiation-induced herpes simplex labialis and response to therapy with peroral and topical formulations of acyclovir. J Infect Dis 1991;163:728-34. 38. Gibson JR, Klaber MR, Harvey SG, Tosti A, Jones D, Yeo JM. Prophylaxis against herpes labialis with acyclovir cream--a placebo-controlled study. Dermatologica 1986;172:104-7. 39. Valtrex: Market Research Report. Data on file. GlaxoSmithKline 2004. 40. Raborn GW, Chan KS, Grace M. Treatment modalities and medication recommended by health care professionals for treating recurrent herpes labialis. J Am Dent Assoc 2004;135:48-54.

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Questions
1. Cold sores appear most frequently on the skin or mucous membrane of the: a. gums b. lips c. cheeks d. mouth e. tongue 2. All of the following statements are true about cold sores except: a. the virus must be acquired via saliva b. Streptococcus sanguis is one of the causes c. they are extremely contagious d. they occur commonly in persons living communally e. they are common in children 3. All of the following statements are true about prodromal symptoms associated with cold sores except: a. tingling and itching are two of the symptoms b. about 25% of cold sore episodes with a preceding prodrome abort early c. they precede the appearance of maculopapular ulcers by 1-24 hours d. they occur in up to 40% of cold sore sufferers e. prolonged prodromal symptoms are probably infrequent 4. All of the following statements are true about docosanol except: a. it is a saturated straight-chain alcohol b. it is also active in vitro against adenovirus c. its preferential action is upon lipid-enveloped viruses d. in experimental studies, it inhibits action of the respiratory syncytial virus e. it prevents viral replication by preventing viral entry into the cell 5. All of the following statements are true about docosanol used for treating cold sores except: a. viral resistance has not been reported b. it does not inactivate the virus directly c. it blocks HSV binding to receptors on target cells d. it is most effective if used early in the course of an outbreak e. HSV remains longer on the surface of cells treated with docosanol
6. Which one of the following statements is true concerning a cold sore? a. the area immediately around the lesion is soft b. several vesicles may coalesce to form larger ones c. the hard crust over mature lesions remains 8 to 10 days d. edema persists only 2 to 3 days e. once blisters rupture, the chance for infection becomes minimal 7. A patient with a history of cold sores should be counselled with which of the following points? a. cold sore blisters should be broken to remove the barrier to getting medication to underlying skin b. persons who have eczema are, for some reason, immune to cold sore formation c. cold sores, unlike canker sores, are not painful or discomforting d. lesions are considered healed when the crust disappears and new skin has formed over the area e. whenever healing does not occur within 10 days, you should see a doctor or dentist 8. All of the following statements are true about HSV-1 except: a. humans are the only known host b. it causes most orofacial cold sores c. an intact oral epithelium blocks entrance into the body d. the incubation period, following inoculation, is 2 to 3 days e. primary infections are often subclinical and go unnoticed 9. Stimulants known to incite recurrent cold sore outbreaks include all of the following except: a. ultraviolet radiation b. GI disturbance c. high humidity d. minor infections e. dental treatment 10. HSV-1 remains dormant in the body in what site? a. dorsal root ganglia b. nicotinic synapses c. central presynaptic nerve fibers d. peripheral postsynaptic fibers e. epidural sheath of the spinal cord

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11. A patient with cold sores who asks about the frequency of application of docosanol cream should be counselled to apply it: a. once a day in the morning b. twice daily, in the morning and at bedtime c. immediately after each meal d. five times a day e. every two hours until symptoms subside 12. In a clinical trial reported in this article, the median time-to-healing of cold sores in patients treated with docosanol 10% cream was shortened by how many hours compared to patients receiving placebo treatment? a. 4 hours b. 6 hours c. 12 hours d. 18 hours e. 24 hours 13. Sound advice to pass along to a patient suffering from recurrent cold sores includes all of the following points except: a. Cold sores are also called fever blisters and herpes outbreaks. Cold sores are not the same as canker sores. b. Gently wash the lesion area with a mild soapfree liquid cleanser and pat dry with paper towels. Discard used towels. Wash your hands carefully with a liquid cleanser and water and keep them away from cold sore lesions as much as possible. c. You may take analgesics such as ASA, acetaminophen, or ibuprofen to help relieve the severe pain of cold sores. Be sure to follow the directions for use. Children should not take ASA. d. Despite all caution, remember that it is possible to transmit herpes virus even when no blisters are present. e. Apply products containing skin protectants over the cold sore and on all adjacent, noninvolved areas to help protect them against infection.
14. Holly is a 28-year-old female who presents at the community pharmacy with a small lesion at the corner of her lips. The lesion appears to be excessively red, swollen, and contains fluid. She has had this for the past two days. When should you refer her to see a doctor? a. immediately -- because she looks like she is in pain and the area appears swollen b. when the cold sore lesions break c. if she has a history of cold sore lesions appearing a few times over this year d. if the cold sore lesions start to itch e. if other cold sore lesions start to appear in the general area of the original one 15. Holly is an avid skier and is constantly on the ski hills teaching skiing and as for her own leisure. Which of the following is/are not factors that can lead to cold sores? a. fatigue b. ultraviolet radiation c. chilly conditions d. acidic food such as citrus fruits, tomatoes, pickles, or salty snacks e. windburn 16. Holly is worried that she may pass on her cold sore virus to her young children (aged 9 months and 3 years). Which of the following is false? a. HSV-1 runs in the family. It is hereditary. b. Babies generally have anti-HSV antibodies from their mothers when they are born. c. HSV-1 is usually caught in early childhood between 6 months and 14 years of age. d. HSV-1 infections are prevalent in areas of communal residences or socializing such as daycare centres and primary school classrooms. 17. You counsel Holly on the best way to minimize the possibility of infecting her children. Identify which statement is true: a. She should break the lesions immediately to hasten the healing process. b. There is nothing you can recommend for her -- she should go see her doctor immediately for something to help with her cold sores. c. She should continue to kiss and rock her children to sleep. d. She should ensure all her lesions are washed with a mild soap-free liquid cleanser and patted dry with paper towels that are then discarded.

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Recurrent Herpes Labialis

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Recurrent Herpes Labialis

James Paterson, PhD Mona Kwong, MSc Pharm

Asessment and Non-prescription Treatment

All material 2005 MediResource Inc.

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Figure 1. Stages of a typical cold sore outbreak

Adapted from Barbarash 2001.

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Table 1. Developmental stages of recurrent HSV-1 outbreaks

Small, solid, raised lesions with inflammation

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

1.3 Distinguishing cold sores from other orofacial lesions

Table 2. Factors known to activate recurrent herpes infections 2,7,8,11

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Table 3. Differentiating cold sores from canker sores

1014 days; healing without scarring

Figure 2. Visual differences between cold sore and canker sore

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

2.1 Symptom support treatments

Table 4. Examples of non-prescription products used for cold sores

Blistex Lip Medex

Moisturizer; supports skin barrier; local anaesthetic

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Product Chapstick SPF15

Manufacturer Whitehall-Robins Inc.

Sunscreen; moisturizer; supports skin barrier Labello Regular

Beiersdorf Canada Inc.

Moisturizer; supports skin barrier Labello Med

Beiersdorf Canada Inc.

Moisturizer; supports skin barrier Life Brand Cold Essentials

Norwood Packaging Ltd.

Johnson & Johnson

Local anaesthetic Lipactin

Novartis Consumer Health Canada

Medibrands Inc. Local anaesthetic Zila Pharmaceuticals Inc.

Local anaesthetic, exfoliant

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

2.2 Products with possible anti-viral activity

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Figure 3. Proposed mechanism of action for docosanol

2.3 Viral entry blocking agents

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

2.4 Unsafe or ineffective non-prescription remedies

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

4.2 Role of the pharmacist

4.3 Patient information

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Table 5. Patient information on cold sores and their treatment

4.4 Roles of other healthcare practitioners

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Table 6. Patient information on treatment of cold sores with non-prescription products

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Figure 4. Pharmacist treatment algorithm for RHL

Patient with suspected HSL Patient with suspected HSL

Self-care of canker sores

Are lesions healed after 14 days?

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment

Recurrent Herpes Labialis: Assessment and Non-prescription Treatment