Swollen lymph node herpes

Sore Throat Herpes

Can Herpes Cause a Sore Throat?

Herpes is an infection caused by the herpes simplex virus. Although inflammation of the affected site and fluid-filled sores are the most common symptoms of a herpes outbreak, some people may also experience sore throat, fatigue, and headache. There are two types of herpes — herpes simplex 1 (HSV1) and herpes simplex 2 (HSV2). This article will go into more detail about these types, their symptoms, and treatment options.

Herpes Simplex 1

Herpes simplex type 1 (oral herpes) affects more than 50% of the U.S. adult population. Commonly referred to as either cold sores or fever blisters, herpes simplex type 1 can cause sores on or around the mouth, nose, chin, or cheeks.

Signs and Symptoms | Herpes | Sore Throat

According to the Center for Disease Control, “Most people who have herpes have no, or very mild symptoms. You may not notice mild symptoms or you may mistake them for another skin condition, such as a pimple or ingrown hair. Because of this, most people who have herpes do not know it.”

Other symptoms include:

  • A tingling or itching sensation at the outbreak site.

  • One or more fluid-filled blisters

  • Fever

  • Muscle aches

  • Swollen lymph nodes

  • Sore throat


Oral herpes is highly contagious and can be transmitted through direct contact between the affected area and mucous membranes or broken skin.

During an outbreak it is recommended that you do not:

  • Kiss others on the mouth or face

  • Perform oral sex

  • Spend extended periods of time in the sun, as UV rays can make herpes symptoms worse

  • Share drinks, food, or eating utensils

  • Touch the affected area, as it can be easily spread across other areas of the body

Herpes Simplex 2

Herpes simplex type 2 (genital herpes) affects 1 out of 6 people aged 14 to 49 years. Genital herpes can cause sores on or around the genital area and rectum, and can affect both men and women.

Signs and Symptoms

The symptoms of genital herpes are similar to those of oral herpes and can include flu-like symptoms such as headache, sore throat, and fever.


Genital herpes can be transmitted through vaginal or anal sex, and can also be passed from someone’s genitals to someone’s mouth during oral sex.

To lower your risk of herpes simplex 2 infection:

  • Limit your sexual partners

  • Always use condoms during sexual intercourse

  • Do not have sex (even with a condom) if you or your partner have an outbreak

  • Remember that herpes simplex 1 and 2 can be contagious even with no visible symptoms

FastMed Urgent Care provides personal and cost-effective medical care within an hour. If you think you may be experiencing symptoms associated with a herpes outbreak, including sore throat and flu-like symptoms, visit your local FastMed clinic today.

Herpes in Throat

Table of Contents

Herpes in the throat, also known as herpes esophagitis is when herpes simplex virus invades the esophagus.

Herpes esophagitis is a viral infection caused by the herpes simplex virus.

There are two types of herpes virus HSV-1 and HSV-2:

  • HSV-1 is more commonly associated with herpes in the throat. This virus is the same one that causes cold sores and it is generally transmitted by mouth-to-mouth contact, but can also be passed through oral sex. It is also known as oral herpes.
  • HSV-2 is the primary cause of genital herpes, but can also cause oral herpes. It is typically passed through vaginal, anal, and oral sex.

Who is at Risk?

The herpes simplex virus affects two thirds of the global population, although herpes esophagitis isn’t very common in healthy people.

People who have weakened immune systems are more at risk to contracting herpes of the throat, they include people who have or have had:


Leukemia or other cancers

An organ transplant


Any illness that compromises your immune system

Any autoimmune disease, such as rheumatoid arthritis or lupus

People who abuse alcohol

People who take long-term antibiotics

Read: How to Get Tested for Herpes and Why it Matters


The primary symptoms of herpes in the throat are:

Open sores in the mouth and throat (herpes labialis)

Difficulty swallowing


Chest pain

Other secondary symptoms are:

Joint pain



Not feeling well

Read: What Does Herpes Look Like


Herpes esophagitis is very rare and can be avoided by practicing safe sex. Ways to ensure you are not at risk of spreading or contracting the herpes virus are:

Using a condom

Using dental dams

Always informing your partner if you’re experiencing a herpes outbreak

Refraining from sexual relations while experiencing a herpes outbreak

The herpes virus is most contagious during an outbreak, but can be transmitted when no obvious symptoms are present.


There is no cure for herpes, however you should get treated as fast as possible if you believe you have it.

There are various medications available to help treat esophagitis caused by the herpes virus. The following antibiotics can help:

acyclovir (Zovirax) famciclovir (Famvir) valacyclovir (Valtrex)

If you believe you are experiencing a herpes outbreak, contact your doctor or a PlushCare doctor to get tested for herpes, confirm your diagnoses and start proper treatment.

To book an appointment with a PlushCare online doctor, click here.

Read More About Herpes in Throat

  • How to get tested for STDs
  • Home Remedies for Herpes
  • How Long Will My Herpes Outbreak Last?


Cold sore (herpes simplex virus)

About cold sores

Cold sores that keep coming back (recurrent) are shorter and less severe than a first infection.

Most people with recurrent herpes lip infections have two or more outbreaks (episodes) per year.

A minority of people can have six or more outbreaks per year. Infections in the mouth can be more severe and last two to three weeks.

Symptoms of cold sores

You may not have any symptoms when you first become infected with the virus (the primary infection). An outbreak of cold sores may occur some time later and keep coming back (recurrent infection).

If the primary infection does cause symptoms, they can be quite severe.

Herpes simplex virus primary infection

In children

Symptoms of the primary infection are most likely to develop in children younger than five years old. Symptoms include:

  • swollen and irritated gums with small, painful sores in and around the mouth – this is known as herpes simplex gingivostomatitis
  • sore throat and swollen glands
  • producing more saliva than normal
  • high temperature (fever) of 38C (100.4F) or above
  • dehydration
  • feeling sick (nausea)
  • headaches

Herpes simplex gingivostomatitis usually affects young children, but adults can also develop it. It can last 10 to 14 days, with the sores taking up to three weeks to heal. Gingivostomatitis doesn’t usually recur after the primary infection.

In adults

Primary herpes simplex viruses are rare in adults. But the symptoms are similar to those experienced by children.

Symptoms include:

  • you’ll usually have a sore throat with or without swollen glands
  • you may also have bad breath (halitosis) and painful sores in and around your mouth – these can develop into ulcers with grey or yellow centres

If you develop the herpes simplex virus at an early age, it may be triggered from time to time in later life. It can cause recurring bouts of cold sores.

After the primary infection, the symptoms are usually reduced to just the cold sores themselves.

Recurrent infections (cold sores)

Recurrent infections:

  • usually last for less time and are less severe than the primary infection
  • the only symptom is an outbreak of cold sores, although you may also have swollen glands
  • an outbreak of cold sores usually starts with a tingling, itching or burning sensation around your mouth
  • small fluid-filled sores then develop, usually on the edges of your lower lip
  • if you have frequent recurrent infections, you may develop cold sores in the same place every time – they may grow in size and cause irritation and pain
  • to start with they may ooze before crusting or scabbing over within 48 hours of the initial tingling sensation

Most cold sores, in a recurrent infection, disappear within 7 to 10 days without treatment and usually heal without scarring.

When to visit your GP

You only need to visit your GP if:

  • you’re unsure whether it’s a cold sore
  • it’s severe and spreading further than just the lip
  • a cold sore hasn’t healed after 10 to 14 days for a first episode, or seven to 10 days for a recurrence

Treating cold sores

Recurrent cold sores usually clear up by themselves without treatment within 7 to 10 days.

Antiviral creams and other treatments are available over the counter from pharmacies without a prescription.

If used correctly, these can help ease your symptoms and speed up the healing time.

To be effective, these treatments should be applied as soon as the first signs of a cold sore appear. This is when you feel a tingling, itching or burning sensation around your mouth. Using an antiviral treatment after this initial period is unlikely to have much of an effect.

Ask your pharmacist if you need information about treatments for cold sores.

If your GP thinks it is necessary, antiviral tablets may be prescribed for severe cases.

Complications of cold sores

Cold sores are usually mild, but may cause complications in rare cases. People with weak immune systems caused by illness or treatments such as chemotherapy are particularly at risk of complications.

If the infection affects the mouth or throat, dehydration sometimes occurs if drinking fluids becomes painful. Young children are particularly at risk of becoming dehydrated.

Preventing infection

The herpes simplex virus – or “cold sore virus” – is highly contagious. It can be easily passed from person to person by close direct contact.

After someone has contracted the virus, it remains inactive (dormant) most of the time.

It’s not possible to prevent infection with the virus or prevent outbreaks of cold sores. But you can take steps to minimise the spread of infection.

Cold sores are at their most contagious when they burst (rupture). They stay contagious until they’re completely healed. Avoid close contact with others until your cold sore has completely healed and disappeared.

There’s no need to stay away from work or miss school if you or your child have a cold sore.

You can help minimise the risk of the cold sore virus spreading and cold sores recurring by:

  • avoid touching cold sores unless you’re applying cold sore cream – creams should be dabbed on gently rather than rubbed in, as this can damage your skin further
  • always wash your hands before and after applying cold sore cream and after touching the affected area
  • don’t share cold sore creams or medication with other people as this can cause the infection to spread
  • don’t share items that come into contact with the affected area, such as lipsticks or cutlery
  • avoid kissing and oral sex until your cold sores have completely healed
  • be particularly careful around newborn babies, pregnant women and people with a low immune system, such as those with HIV or those having chemotherapy
  • if you know what usually triggers your cold sores, try to avoid the triggers – for example, a sun block lip balm (SPF 15 or higher) may help prevent cold sores triggered by bright sunlight
  • Find out more about cold sores on the NHS website

Herpes: your questions answered

What is herpes?

Herpes is a common, life-long infection caused by the herpes simplex virus (HSV) and generally transmitted through skin-to-skin contact. The symptoms of herpes can vary greatly, mainly depending on whether a person is experiencing their first episode or a recurrence. Once infected you may have symptoms returning on and off for years.

A commonly recognised symptom is the appearance of small, painful blisters – also called vesicles – on the skin. Herpes can appear on the lips (oral herpes), genitals (genital herpes) or on other parts of the body (non-genital herpes).

The herpes simplex virus belongs to a larger family of viruses that cause chickenpox, shingles and glandular fever.

There are 2 types of herpes simplex virus — herpes type I (HSV-1) and herpes type 2 (HSV-2). Herpes type 1 is the virus that most commonly causes cold sores on the lips or face. While often transmitted during childhood through close physical contact, this infection can be transmitted at any age. It can also be transmitted to the genitals through direct skin-to-skin contact, often via oral sex. Although HSV-1 infection is common, many people with the infection do not experience symptoms.

HSV-2 is responsible for the majority of genital herpes and is commonly transmitted through sexual contact — anyone who is sexually active can get herpes type 2. Genital herpes is thought to be one of the most common sexually transmitted infections in Australia.

The primary difference between the 2 viral types is preference of location. Herpes type 1 is usually located in the trigeminal ganglion, a collection of nerve cells near the ear. From there, it tends to recur on the lips or face. In contrast, herpes type 2 is usually found in the sacral ganglion at the base of the spine. From there, it recurs in or around the genital area.

The 2 types of herpes simplex virus behave somewhat differently depending on whether or not they are residing in their preferred site.

Either viral type can reside in either or both parts of the body and infect oral and/or genital areas.

How do you know if you have genital herpes?

Many people will have no noticeable symptoms following infection and will not even realise that they have come into contact with the virus. They may notice symptoms only at a later date. People can be infected with genital herpes and pass it on to others even though they have no symptoms themselves.

For others, the first symptoms of genital herpes show up from 2 to 21 days after coming into contact with the herpes virus. This first episode of genital herpes is frequently the most severe. When you first come into contact with the virus, your immune system has not had time to develop protective antibodies, leading to the virus multiplying rapidly and causing significant symptoms.

In a severe first episode of genital herpes, you may notice the following symptoms.

  • Your lymph glands (the glands under your arms, on your neck and in your groin) may be swollen.
  • You may have flu-like symptoms such as sore muscles, tiredness, headaches, fever and chills.
  • You may have swelling, pain or itching around the genitals, possibly followed by painful red spots that can form blisters.
  • Your blisters may burst to form open sores or ulcers, which will later crust over and heal.
  • You may experience pain when urinating due to the tenderness in your genital area.

Herpes of the anus or rectum may also result in rectal and lower back pain, an urgent need to pass faeces, bloody or mucous discharge, constipation and blisters on the skin area around the anus.

How is herpes diagnosed?

Accurate diagnosis of herpes is essential to ensure you receive the correct treatment.

People may mistake their herpes outbreaks for insect bites, yeast infections, jock itch, ingrown hair follicles, haemorrhoids, abrasion or razor burn. Accurate diagnosis is made most easily and correctly at the time of an active herpes infection, preferably the first time the symptoms appear.

There are several diagnostic tests available for herpes, requiring either a swab from a herpes blister or a blood test. The blood test can tell if you have been exposed to the virus in the past, but will not tell you if a particular sore is caused by herpes, or reliably differentiate between HSV-1 and HSV-2. Swabs can tell you if the sore is herpes or not, and what type it is, but can’t tell if it is an initial infection or a recurrence. If you think you may have contracted the virus, see your doctor for testing.

How is herpes treated?

There is no cure for herpes – the virus just has periods of activity and inactivity within your body.

Usually symptoms will heal within 2 to 4 weeks and cause no long-term damage. However, if you experience significant pain with any outbreak you should ask your doctor about antiviral medicines. These can greatly reduce the length and severity of outbreaks and may reduce the risk of you transmitting the infection to a partner. Adverse side-effects from these medicines are rare, although you may get headaches and nausea.

There are other things you can do to relieve symptoms including taking painkillers such as paracetamol, bathing the blisters with warm salty water and dabbing a local anaesthetic ointment on the affected area.

What are some of the common emotions people with herpes experience?

Fear, shock, worry and guilt are common reactions of people who discover they have herpes. This shock sometimes makes it hard to recall any advice given by a doctor or others when first learning about the infection. Doctors understand this, so it may be worthwhile revisiting your doctor to further discuss measures for managing your herpes. Your local sexual health clinic can also provide you with information about support groups and counsellors in your local area.

Do I need to tell my partner I have herpes?

Yes. It is important to discuss your genital herpes with a current or potential partner before having sex. That way, you can work together to reduce the chance of transmission, such as through use of condoms. It may be difficult for you to broach the issue at first, but once the topic is out in the open it will be easier to deal with situations that arise, e.g. you need to let your partner know that there may be times when you cannot have sex.

Sometimes a prospective partner may withdraw from a person with herpes because of their own concerns. However, most people respond well and appreciate the respect that you have shown them, although this may take time. Some partners may already have experienced herpes — it may be worth your partner having a blood test to see if they have already contracted the herpes virus, in which case they are at no further risk — you cannot catch it twice.

Will I get genital herpes again?

Some people have no further episodes or symptoms of herpes. This is called inactive infection, when the virus is hidden in the body and is not infectious.

The symptoms of genital herpes do recur in some people, although a second or third episode is not usually as severe as the first. This is called an active infection and can occur when the immune system is at a low, for example, during times of stress, illness or menstruation, from anything that causes skin irritation, such as friction from prolonged sexual intercourse, but often for no obvious reason.

When a person has genital herpes, the virus ‘sleeps’ in the bundle of nerves at the base of the spine. When the virus reactivates, it travels down nerve paths to the surface of the skin, sometimes causing an outbreak.

The nerves in the genitals, upper thighs and buttocks are connected. So a person can also experience outbreaks in any of the following areas:

  • vagina;
  • vulva;
  • thighs;
  • penis;
  • scrotum;
  • testicles;
  • anus; or
  • buttocks.

What other help is available?

You may experience mixed emotions and confusion after discovering you have genital herpes. A counsellor may prove helpful. Counsellors experienced in genital herpes can often be contacted through sexual health clinics. They have an understanding of both the medical and emotional issues associated with genital herpes.

Support groups

Herpes support groups offer a confidential environment for discussing issues and information with others in a similar position. While some groups are facilitated by a counsellor, others have a more social focus. Contact your local sexual health clinic for information about support groups in your area.


Apart from general healthcare websites such as myDr, there are many sites on the Internet offering information, news, chatgroups and meeting services specifically for people with genital herpes. Please note that the information may not necessarily be accurate so you should verify the information you download from the Internet with your doctor.

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Last Reviewed: 26/11/2012


Genital Herpes Symptoms and Diagnosis

What Are Genital Herpes Outbreaks Like?

Lots of people who have been infected with either HSV-1 or HSV-2 don’t know it because they have never noticed any signs or symptoms.

People often mistake a herpes outbreak for another problem. You may think you have the flu, another STD, or that you have pimples or ingrown hairs, when in fact you have genital herpes symptoms.

Primary Herpes Outbreak

If you do develop symptoms, your first outbreak will most likely start 2 to 20 days after you get infected. In some people, though, a first outbreak occurs years after that first infection. Generally, first outbreaks last two to four weeks. Then the sores and symptoms fade away, but the virus remains in your body in a dormant or quiet state much of the time. That lingering virus can cause later outbreaks, but usually the first is the worst.

During a primary outbreak of genital herpes, you may experience symptoms that mimic the flu, such as:

  • Fever
  • Achy muscles
  • Headaches
  • Swollen lymph nodes in the groin
  • Malaise, a general feeling of distress

Later Outbreaks

Repeat outbreaks are especially common in the first year of a herpes infection. If you have a repeat outbreak, it may begin with some low-level warning symptoms during a period called a prodrome. A few hours or a few days before a repeat outbreak, you may feel itchy, tingly, or burning sensations in your genitals. These sensations generally arise where the infection first entered your body. Your legs, buttocks, and lower back may hurt.

“Most people do have a prodrome with a recurrent outbreak, with tingling and burning in their skin. Then they usually break out in sores in the same place over and over when they actually become symptomatic,” says I. Cori Baill, MD, an obstetrician-gynecologist and an associate professor at the University of Central Florida College of Medicine in Orlando.

For most people, recurrences are somewhat less painful and shorter than the initial outbreak. The frequency of any later outbreaks, or recurrences, varies from person to person. Outbreaks may not occur at all or they may arise several times a year, or less often. Sores that occur in recurrences usually heal faster than the sores associated with a first episode of illness.

In many cases, outbreaks become more widely spaced as years pass.

What are the symptoms of herpes simplex?

In some people (mostly children) an initial HSV-1 infection may cause fever, painful swelling, and open sores on the gums and inside the cheeks, or a painful sore throat. When these herpes symptoms do develop, they usually begin two to twelve days after exposure to someone with HSV-1.

Symptoms of a first episode of HSV-2 usually appear within two to ten days of exposure to the virus and last an average of two to three weeks. Early symptoms can include an itching or burning sensation; pain in the legs, buttocks, or genital area; vaginal discharge; or a feeling of pressure in the abdominal region. Within a few days, sores (lesions) appear at the site of infection. Lesions also can occur on the cervix in women or in the urinary passage in men. These small, red bumps may develop into blisters or painful open sores. Over a period of days, the sores become crusted and then heal without scarring. Other symptoms that may accompany a primary episode of genital herpes can include fever, headache, muscle aches, painful or difficult urination, vaginal discharge, and swollen glands in the groin area.

After the initial infection in the skin or mucous membranes, the virus travels to the sensory nerves at the end of the spinal cord and makes a home. In most people, the virus becomes dormant (inactive). In others, however, it can be reactivated by trauma or stress, or whenever else the immune system fails to keep it in check. When the virus becomes reactivated, it travels along the nerves to the skin, where it multiplies on the surface at or near the site of the original herpes sores, causing new sores to erupt. It can also reactivate without causing any visible sores.

Herpes Simplex Virus Lymphadenitis: Case Report and Review of the Literature


Localized or regional necrotizing lymphadenitis is an extremely uncommon manifestation of herpes simplex virus (HSV) infection. We report a case of necrotizing HSV lymphadenitis in a patient with both common variable immunodeficiency and natural killer cell deficiency and review the literature on this unusual complication of HSV infection.

Herpes simplex virus (HSV) is a well-known cause of gingivostomatitis, herpes labialis, genital ulcers, and encephalitis. Lymphadenopathy in HSV infection may occur in association with disseminated infection with multiorgan involvement , as generalized lymphadenopathy associated with an erythematous rash with no other organ involvement, , or rarely as generalized or regional lymphadenopathy with or without associated regional skin rash and no other evidence of disease . The following case report describes a patient with common variable immunodeficiency (CVID), natural killer (NK) cell deficiency, and massive cervical lymphadenopathy in response to infection with HSV.

Case Report

A 43-year-old male flight attendant was admitted to Harbor—UCLA Medical Center in July 1996 with an enlarging left neck mass associated with fevers, chills, night sweats, and a weight loss of 25 lbs. over the preceding 4 months. He had a history of chronic sinusitis, otitis media, chronic interstitial lung disease diagnosed by open lung biopsy, cataract of the right eye secondary to herpes zoster infection 3 years prior, recurrent genital herpes, and treated syphilis.

The patient first noted the neck swelling in April 1996. CT scan of the neck was obtained, revealing bilateral cervical and left submandibular lymphadenopathy. CT scan of the abdomen showed hepatosplenomegaly and abdominal and para-aortic lymphadenopathy. An excisional biopsy of the left neck mass performed at an outside hospital revealed a dense mass of matted lymph nodes, with histologic evidence of lymphoid infiltration of the sternocleidomastoid muscle with central necrosis and surrounding reactive hyperplasia; culture results were negative for bacteria, mycobacteria and fungi. A bone marrow biopsy revealed a single cluster of lymphohistiocytes, with no evidence of lymphoma. The patient’s cervical lymphadenopathy increased in size over 2 months. In June 1996, the patient was readmitted with fever of 38.9°C, chills, and night sweats. An MRI scan of the neck revealed massive anterior and posterior cervical lymphadenopathy, with displacement of the trachea and left carotid artery. Blood, mycobacterial, and mycology cultures were sterile. Delayed type hypersensitivity skin test was reactive to mumps. The patient defervesced spontaneously and was discharged home.

The patient was then admitted to our hospital in July of 1996 for progressive enlargement of the neck mass. Physical examination revealed a temperature of 37.7°C; a warm, erythematous, tender neck mass was noted to extend from the left lower mandible to just below the pinna to the base of the neck (figure 1A). Palpation of the mass revealed markedly indurated, hard, fixed, and matted submandibular and cervical lymph nodes. The remainder of the examination was noteworthy for the presence of a firm, tender, 2-cm × 2-cm left axillary lymph node, firm, 1-cm inguinal lymph nodes; bibasilar dry crackles on lung examination, and hepatosplenomegaly. A CT scan of the neck revealed extensive soft-tissue swelling and multiple rim-enhancing masses in the left cervical region extending from the inferior portion of the left parotid gland to the supraclavicular level, consistent with necrotic lymph nodes or multiple abscesses. A CT scan of the chest showed bilateral interstitial lung disease with fibrosis at the bases. Pulmonary function tests demonstrated obstructive and restrictive lung disease with a markedly reduced diffusion capacity. An abdominal CT scan again showed marked splenomegaly, para-aortic lymphadenopathy, and a 1.5-cm left adrenal mass.

Figure 1

Left, Appearance at time of diagnosis. Right, Appearance after 18 months of acyclovir and intravenous immunoglobulin (a full-color version is available in the on-line edition of this article).

Figure 1

Left, Appearance at time of diagnosis. Right, Appearance after 18 months of acyclovir and intravenous immunoglobulin (a full-color version is available in the on-line edition of this article).

Serologic tests for HIV, syphilis, coccidioides, histoplasmosis, cryptococcosis, toxoplasmosis, Bartonella henselae, brucellosis, Epstein-Barr virus, and cytomegalovirus were negative. HIV-1 RNA PCR was also negative. Routine urine, sputum, and blood cultures were negative, as were mycology and mycobacterial cultures. An excisional biopsy of a left supraclavicular lymph node was performed.

Histological examination of the biopsy material revealed necrotizing lymphadenitis consistent with herpetic lymphadenitis (figure 2A). Immunohistochemical stains using polyclonal antibodies against HSV-1 and HSV-2 virus, respectively, were positive (figure 2B, only to HSV-2 shown). Electron microscopy (figure 2C) revealed intranuclear and intracytoplasmic virus particles morphologically consistent with herpesvirus. PCR (using primers to the major HSV glycoprotein, g8, at the University of Washington Medical Center) and culture (using fluorescent antibody) confirmed the presence of HSV-2. Acyclovir (10 mg/kg iv q8h) was initiated in early August 1996. Within 2 days, the patient defervesced and had diminished erythema and tenderness of the neck mass. He was discharged from the hospital on a prolonged course of oral acyclovir.

Figure 2

A, Sections of the lymph node display extensive geographic zones of eosinophilic necrosis containing disintegrated neutrophils, nuclear debris, ghost cells with granulomatous reaction at the periphery where characteristic intranuclear eosinophilic inclusions (Cowdry type A) with margination of chromatin and halo formation (short arrow) are present. Others exhibit pale or slightly acidophilic, homogenous, hyalin-like bodies that fill an enlarged nucleus and are circumscribed by a thin rim of marginated chromatin giving a ground-glass appearance (long arrows). Hematoxylin-eosin stain, ×320). B, Immunohistochemical stain, using polyclonal antibodies against HSV-2, which shows strong reactivity in both the nucleus and the cytoplasm for the infected cells (arrows), which are located especially near the periphery within the necrotic zones. (Avidin-biotin-immunoperoxidase stain, ×320). C, Electron microscopic examination reveals numerous intranuclear or intracytoplasmic virus particles. These particles are either in the form of nucleocapsid (characterized by a dense core which is separated from the capsid by a clear halo), or empty capsid. Other virus particles have envelopes and are 90–100 nm in diameter. The ultrastructures are consistent with the viruses of the herpes group. (×37, 500).

Figure 2

A, Sections of the lymph node display extensive geographic zones of eosinophilic necrosis containing disintegrated neutrophils, nuclear debris, ghost cells with granulomatous reaction at the periphery where characteristic intranuclear eosinophilic inclusions (Cowdry type A) with margination of chromatin and halo formation (short arrow) are present. Others exhibit pale or slightly acidophilic, homogenous, hyalin-like bodies that fill an enlarged nucleus and are circumscribed by a thin rim of marginated chromatin giving a ground-glass appearance (long arrows). Hematoxylin-eosin stain, ×320). B, Immunohistochemical stain, using polyclonal antibodies against HSV-2, which shows strong reactivity in both the nucleus and the cytoplasm for the infected cells (arrows), which are located especially near the periphery within the necrotic zones. (Avidin-biotin-immunoperoxidase stain, ×320). C, Electron microscopic examination reveals numerous intranuclear or intracytoplasmic virus particles. These particles are either in the form of nucleocapsid (characterized by a dense core which is separated from the capsid by a clear halo), or empty capsid. Other virus particles have envelopes and are 90–100 nm in diameter. The ultrastructures are consistent with the viruses of the herpes group. (×37, 500).

Because of the patient’s history of interstitial lung disease, chronic sinusitis, otitis media, and HSV lymphadenitis, an immunologic investigation was initiated. Serum IgG and IgM concentrations were markedly decreased (table 1). NK cell studies showed reduced number (table 2) and function (table 3). HIV PCR (Roche, Amplicor) was negative. Complement levels and the Nitroblue tetrazolium dye reduction test were within normal limits. Monthly iv immunoglobulin at a dose of 25 g was begun in September 1996. The patient has had no further bacterial infections, and the necrotizing lymphadenitis has completely resolved after 18 months (figure 1B).

Table 1

Patient’s quantitative immunoglobulin values.

Table 1

Patient’s quantitative immunoglobulin values.

Table 2

Summary of patient’s flow cytometry analysis.

Table 2

Summary of patient’s flow cytometry analysis.

Table 3

Natural killer cell–mediated lysis: patient vs. normal control.

Table 3

Natural killer cell–mediated lysis: patient vs. normal control.


HSV is a DNA virus with 2 serologic types, for which man is the only natural host . Serotype 1 is more frequently associated with nongenital infection, whereas serotype 2 is more commonly associated with genital disease , though significant overlap exists. The virus has the capacity to (1) invade and replicate in the CNS and (2) establish latent infection . HSV infection causes primary and recurrent diseases of the skin, mucous membranes, eye, and CNS. In the immunocompromised host, reactivation and dissemination of herpetic lesions can occur, characterized by progressive disease involving the skin, oropharynx, respiratory, and gastrointestinal tracts; however, even in the setting of disseminated infection, HSV lymphadenitis is rare , with only 22 published reports to date (table 4) . Seventeen of the 22 cases occurred in immunocompromised hosts, including 13 patients with a lymphoreticular neoplasm. Eleven of the 13 patients had a prior history of malignancy, and 2 patients developed lymphoma between 5 months and 2 years following a diagnosis of HSV lymphadenitis. To our knowledge, our patient is the only reported case of HSV lymphadenitis occurring in the presence of both CVID and NK cell defect.

Table 4

Summary of 22 cases of herpes simplex lymphadenitis.

Table 4

Summary of 22 cases of herpes simplex lymphadenitis.

CVID is a primary immunodeficiency syndrome that includes several different disorders characterized by defective antibody formation accompanied by decreased serum IgG concentrations and usually by decreased serum IgA and IgM concentrations . B cell maturation is intact, but antibody secretion is impaired . There also appears to be diminished interaction between T cells and B cells as a result of defective T cell signal transduction . Cell-mediated immunity may be impaired in some patients, as evidenced by diminished T cell function and absent delayed-type hypersensitivity .

CVID is one of the most frequent of the primary immunodeficiency diseases , with an estimated prevalence of 1 per 50,000–1 per 200,000 . The disease affects men and women equally and usually presents in the second or third decade of life . Various inheritance patterns for CVID have been noted, though sporadic cases are most common . Patients with CVID typically present with recurrent bacterial sinopulmonary infections; many cases are identified only after severe chronic obstructive lung disease and bronchiectasis have developed . Recurrent mucocutaneous and generalized herpes simplex infections are common, although the prevalence of infection is not significantly higher than in the general population . The frequency of reactivated herpes zoster attacks is higher than normal in patients with CVID, developing in ∼20% of patients . Severe cytomegalovirus infections of the gastrointestinal tract have also been reported in a small number of patients . CVID patients are highly susceptible to enteric infections (Salmonella, Shigella, Campylobacter, rotavirus, chronic Giardia lamblia infections).

Other infectious agents reported to cause disease in this population include mycoplasma, Pneumocystis carinii, mycobacteria, various fungi, and enteroviral infection with chronic meningoencephalitis and a dermatomyositis-like syndrome .

Patients with CVID are highly predisposed to develop malignant lymphoreticular and gastrointestinal conditions, with a 50-fold increased risk of gastric carcinoma, and a 30 to 400-fold increased risk of lymphoma . Consequently, patients with CVID should be aggressively screened and closely monitored for the development of malignancy .

Our patient not only had CVID but also had a defect in NK cell number and activity. NK cells are a distinct subset of lymphocytes that contain cytolytic cytoplasmic granules that nonspecifically kill tumor cells and virus-infected cells . These cells attack autologous and allogeneic target cells quickly, without the usual requirements for antigen processing and antigen presentation for activation . Biron et al. have reported a case of recurrent herpesvirus infection in a patient with selective NK cell deficiency. It is conceivable that the massive HSV cervical lymphadenitis in our patient is the result of the diminished number and function of NK cells demonstrated during his work-up.


Even in the setting of generalized HSV infection, lymphadenitis is rare. Our review of the literature suggests that HSV lymphadenitis should be considered in the differential diagnosis of localized or regional lymphadenopathy in the immunocompromised host. Generalized, severe, and chronic HSV lymphadenitis should trigger an immunologic work-up, evaluating B cell defects such as CVID, T cell defects and NK-cell defects. To our knowledge, this is the first case of HSV lymphadenitis occurring in a patient with both CVID and NK-cell deficiency.


We thank Dr. Karl Gaal and Dr. Priya Gulati (Department of Pathology, Harbor—UCLA Medical Center, Los Angeles) for their careful review of the histopathologic specimens and electron microscopy photomicrographs, as well as Bonnie Ank, Dr. E. Richard Stiehm, Patricia Hultin, Dr. Beth Jamieson, and Dr. Janis Giorgi (posthumous), of UCLA School of Medicine, for their analysis of NK-cell quantitation and function. We also thank Dr. Hamid Hussain for his contribution on the discussion about the immunologic aspects of CVID and NK-cell defect.

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Cold Sores

Topic Overview

What are cold sores?

Cold sores, sometimes called fever blisters, are groups of small blisters on the lip and around the mouth. Often the first sign of a cold sore is a spot that tingles, burns, or itches. A blister usually forms within 24 hours. The skin around the blisters is often red, swollen, and sore. The blisters may break open, leak a clear fluid, and then scab over after a few days. They usually heal in several days to 2 weeks.

What causes cold sores?

Cold sores are caused by the herpes simplex virus (HSV). There are two types of herpes simplex virus: HSV-1 and HSV-2. Both virus types can cause sores around the mouth (herpes labialis) and on the genitals (genital herpes).

The herpes simplex virus usually enters the body through a break in the skin around or inside the mouth. It is usually spread when a person touches a cold sore or touches infected fluid—such as from sharing eating utensils or razors, kissing an infected person, or touching that person’s saliva. A parent who has a cold sore often spreads the infection to his or her child in this way. A person can spread the virus to someone else a few days before the sore appears until the sore is completely healed. Cold sores can also be spread to other areas of the body.

What are the symptoms?

The first symptoms of cold sores may include a spot that tingles, burns, or itches around your mouth and on your lips. You may also have a fever, a sore throat, or swollen glands in your neck or other parts of the body. Small children sometimes drool before cold sores appear. After the blisters appear, the cold sores usually break open, leak a clear fluid, and then crust over and disappear after several days to 2 weeks. For some people, cold sores can be very painful.

Some people have the virus but don’t get cold sores. They have no symptoms.

How are cold sores diagnosed?

Your doctor can tell if you have cold sores by asking you questions to find out whether you have come into contact with the virus and by examining you. You probably won’t need any tests.

How are cold sores treated?

Cold sores will usually start to heal on their own within a few days. But if they cause pain or make you feel embarrassed, they can be treated. Treatment may include skin creams, ointments, or sometimes pills. Starting treatment right away may get rid of the cold sores only 1 to 2 days faster, but it can also help ease painful blisters or other uncomfortable symptoms.

The herpes simplex virus that causes cold sores can’t be cured. After you get infected, the virus stays in your body for the rest of your life. If you get cold sores often, treatment can reduce the number of cold sores you get and how severe they are.

How can you prevent cold sores?

There are some things you can do to keep from getting the herpes simplex virus.

  • Avoid coming into contact with infected body fluids, such as kissing an infected person.
  • Avoid sharing eating utensils, drinking cups, or other items that a person with a cold sore may have used.

After you have been infected with the virus, there is no sure way to prevent more cold sores. But there are some things you can do to reduce your number of outbreaks and prevent spreading the virus.

  • Avoid the things that trigger your cold sores, such as stress and colds or the flu.
  • Always use lip balm and sunscreen on your face. Too much sunlight can cause cold sores to flare.
  • Avoid sharing towels, razors, silverware, toothbrushes, or other objects that a person with a cold sore may have used.
  • When you have a cold sore, make sure to wash your hands often, and try not to touch your sore. This can help keep you from spreading the virus to your eyes or genital area or to other people.
  • Talk to your doctor if you get cold sores often. You may be able to take prescription pills to prevent cold sore outbreaks.

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