Patient Presentation This 61-year-old patient presented with a 3-day history of vesicles and crusts on the forehead. She reports a history of a minor trauma to the forehead, which occurred several days before she developed a burning sensation and mild tenderness on her forehead, followed by the eruption of vesicles. She denied fevers, headache, backache, chills, vomiting or severe abdominal pain. She reported no ocular symptoms. Her past medical history was unremarkable. The patient wasn’t sure if she ever developed varicella during childhood, and denied having similar eruptions on any part of her body prior to this episode. Her status of immunity to the varicella couldn’t be determined. She may have been vaccinated for smallpox during childhood, but there was no recent history of revaccination. What is Your Diagnosis? Diagnosis: Herpes Zoster Ophthalmicus (HZO) HZO is defined as cutaneous lesions in the dermatome associated with the ophthalmic division of the trigeminal nerve. HZO represents reactivated varicella zoster virus (VZV), which travels down the ophthalmic nerve from the trigeminal ganglion, taking 3 to 4 days to reach the nerve endings.1,2 The ophthalmic division of the trigeminal nerve, also referred to as the first branch of the fifth cranial nerve (CN V1), has three main parts: the frontal nerve with its two main branches (supraorbital and supratrochlear), the lacrimal nerve, and the nasociliary nerve. The supraorbital and supratrochlear branches of the frontal nerve supply the upper eyelid and forehead and are most often involved in HZO. The lacrimal nerve exits the orbit laterally and supplies the lateral skin of the upper eyelids and lacrimal glands. The nasociliary nerve divides into the posterior ethmoidal, anterior ethmoidal, and infratrochlear nerves. It supplies the tip of the nose through the external nasal nerve, a branch of the anterior ethmoidal nerve and the root of the nose through the infratrochlear nerve. Watch for These Symptoms And Risk Factors Paresthesias or pain along the involved dermatome may precede the development of the vesicles. Cutaneous vesicular eruption over the forehead, lymph node enlargement in the drainage areas, fever, malaise, headache, sometimes neck stiffness, and a red eye follow. Don’t confuse prodromal lymphadenopathy with later reactive adenopathy caused by secondary infection of vesicles. Hutchinson’s sign refers to the presence of VZV vesicles on the side or the tip of the nose, and heralds ocular involvement. However, severe ocular complications can occur with a vesicular rash anywhere on the forehead. Risk factors for reactivation of VZV are diabetes, advancing age, cancer, surgery, radiation, chemotherapy, immune-suppressing drugs, systemic corticosteroid therapy, stress, and congenital or acquired immunosuppression.1,3 Due to the increased severity and risk of patients with HIV, a patient younger than 45 years old presenting with herpes zoster should be considered at risk for HIV.4 The virus may become active again after trauma to the skin from injury or sunburn, as was the case for this patient. Increased age, prolonged prodromal pain and severe acute pain are risk factors for severe post-herpetic neuralgia.5,6 Zosteriform herpes simplex may mimic herpes zoster. Primary varicella, disseminated herpes zoster, disseminated herpes simplex, and other blistering diseases of viral, bacterial or autoimmune etiologies might also be confused with herpes zoster. The Center for Disease Control and Prevention’s Web site (www.cdc.gov) has more information.7, 8 About 20% of adults exposed to the varicella virus during childhood will suffer a recurrence of herpes zoster.10 Remember, VZV can be transmitted to individuals with no prior history of varicella or shingles. Therefore, close contact with active lesions should be avoided. Laboratory Diagnosis In this patient, the diagnosis of HZO was made on clinical bases and was confirmed with polymerase chain reaction (PCR) for VZV DNA. The characteristic cytologic changes and multinucleate giant cells induced by VZV can be seen in Tzanck smears. Punch biopsy provides more reliable material for histological examination. These two laboratory studies don’t distinguish herpes simplex viruses (HSV-1 and HSV-2), and VZV. VZV infection is confirmed by isolation of virus in tissue culture, which often is positive within 48 hours of inoculation, but may take up to 5 days. PCR is growing in uses and availability. It’s a rapid, sensitive, and simple method for diagnosis of VZV. A PCR assay configured to detect vaccinia is under evaluation. Direct fluorescent antibody testing is preferred to a viral culture. It’s also a rapid test, it types the virus, and has a higher yield than a culture will produce. Electron microscopy of lesion material can be useful in differentiating herpes viruses from poxviruses such as vaccinia, but a limited number of centers have this capability. Vaccinia can be readily grown in routine cell culture and identified by referral to a specialty laboratory. Complications of HZO Post-herpetic complications are more common in HZO than in other forms of zoster. Eye involvement poses a risk to vision in the absence of prompt detection and treatment. Iritis, iridocyclitis, secondary glaucoma from uveitis or steroid treatment, keratitis, corneal neovascularization, corneal tissue ulcerations, scarring, and secondary bacterial or fungal infection are possible. In addition, palsy of the third cranial nerve and occasionally of the fourth and sixth cranial nerves may occur.2,9,10 Post-herpetic neuralgia is observed in more than 50% of patients with HZO and can be severe and long lasting; this requires aggressive management.1 Treatment HZO requires aggressive treatment and follow-up monitoring. Obtain ophthalmologic consultation early if the patient has significant ocular symptoms. Local treatment modalities may include warm and moist compresses and ocular lubricants to promote hydration of the cornea and conjunctivae. In addition, capsaicin cream can deplete pain fibers of substance P and reduce pain impulses. Patients must apply this cream regularly four times a day after their lesions have developed a crust, and they should avoid contact with their eyes. Antiviral agents are the cornerstone of systemic treatment of HZO and should be started within 72 hours of onset. Here’s a look at the most common antivirals used to treat HZO, and other typical treatments: Acyclovir (Zovirax). This drug shortens duration of lesions, reduces pain, and leads to faster resolution of lesions. It aborts recurrences if immediately initiated when symptoms surface. The recommended dose for HZO is 800 mg PO five times per day for 7 to 10 days. Valacyclovir (Valtrex). A prodrug, Valtrex rapidly converts to acyclovir. Although more expensive, this drug has a more convenient dosing regimen than acyclovir. It’s given 1000 mg PO t.i.d. for 7 days. Valacyclovir is as effective as acyclovir in preventing ocular complications of HZO, including conjunctivitis, keratitis and pain. Tolerability of both drugs is similar.11,12 Famciclovir (Famvir). Also a prodrug, Famvir is biotransformed into active metabolite penciclovir. The recommended dose for adults is 500 mg PO t.i.d. for 7 days. Famciclovir treatment is comparable to valacyclovir treatment in speeding the resolution of zoster-associated pain and post-herpetic neuralgia, but current wholesale prices indicate that valacyclovir is more cost-effective.12 Systemic corticosteroids are used to decrease pain levels. Use prednisone at 1 to 2 mg/kg PO qd, (not to exceed 60 mg/dl), then taper over 2 weeks as symptoms resolve. Tricyclic antidepressants (for example, amitriptyline [Elavil]). These drugs are often helpful in treating post-herpetic neuralgia. Administer them early in the course of HZO. Analgesics (narcotic agents, acetaminophen, aspirin, or NSAIDs) may also be used. Administer antibiotics that will treat Gram-positive skin flora if you detect a secondary bacterial infection of the vesicles. According to available evidence in patients older than 50 years, antiviral therapy (famciclovir or valacyclovir for 7 days) started within 72 hours of rash onset and/or low-dose amitriptyline (for 90 days) may be offered to reduce the incidence and duration of post-herpetic neuralgia.10,11,12 Our patient was treated with valacyclovir 100 mg PO t.i.d.. Seven days later the pain subsided, and a crust formed on her forehead, replacing previous vesicles. She also didn’t develop any post-herpetic neuralgia. Do you have a case you’d like to see published in this column? If so, please send a write-up (about 600 to 800 words) and an image of the patient’s condition. You may also include a follow-up image of the patient to accompany the discussion portion of the case. Please send materials to: Dr. Amor Khachemoune, Georgetown University Medical Center, Division of Dermatology, 3800 Reservoir Road, NW 5PHC, Washington, DC 20007. Or e-mail them to amorkh@pol.net.
What Caused These Lesions?
Patient Presentation This 61-year-old patient presented with a 3-day history of vesicles and crusts on the forehead. She reports a history of a minor trauma to the forehead, which occurred several days before she developed a burning sensation and mild tenderness on her forehead, followed by the eruption of vesicles. She denied fevers, headache, backache, chills, vomiting or severe abdominal pain. She reported no ocular symptoms. Her past medical history was unremarkable. The patient wasn’t sure if she ever developed varicella during childhood, and denied having similar eruptions on any part of her body prior to this episode. Her status of immunity to the varicella couldn’t be determined. She may have been vaccinated for smallpox during childhood, but there was no recent history of revaccination. What is Your Diagnosis? Diagnosis: Herpes Zoster Ophthalmicus (HZO) HZO is defined as cutaneous lesions in the dermatome associated with the ophthalmic division of the trigeminal nerve. HZO represents reactivated varicella zoster virus (VZV), which travels down the ophthalmic nerve from the trigeminal ganglion, taking 3 to 4 days to reach the nerve endings.1,2 The ophthalmic division of the trigeminal nerve, also referred to as the first branch of the fifth cranial nerve (CN V1), has three main parts: the frontal nerve with its two main branches (supraorbital and supratrochlear), the lacrimal nerve, and the nasociliary nerve. The supraorbital and supratrochlear branches of the frontal nerve supply the upper eyelid and forehead and are most often involved in HZO. The lacrimal nerve exits the orbit laterally and supplies the lateral skin of the upper eyelids and lacrimal glands. The nasociliary nerve divides into the posterior ethmoidal, anterior ethmoidal, and infratrochlear nerves. It supplies the tip of the nose through the external nasal nerve, a branch of the anterior ethmoidal nerve and the root of the nose through the infratrochlear nerve. Watch for These Symptoms And Risk Factors Paresthesias or pain along the involved dermatome may precede the development of the vesicles. Cutaneous vesicular eruption over the forehead, lymph node enlargement in the drainage areas, fever, malaise, headache, sometimes neck stiffness, and a red eye follow. Don’t confuse prodromal lymphadenopathy with later reactive adenopathy caused by secondary infection of vesicles. Hutchinson’s sign refers to the presence of VZV vesicles on the side or the tip of the nose, and heralds ocular involvement. However, severe ocular complications can occur with a vesicular rash anywhere on the forehead. Risk factors for reactivation of VZV are diabetes, advancing age, cancer, surgery, radiation, chemotherapy, immune-suppressing drugs, systemic corticosteroid therapy, stress, and congenital or acquired immunosuppression.1,3 Due to the increased severity and risk of patients with HIV, a patient younger than 45 years old presenting with herpes zoster should be considered at risk for HIV.4 The virus may become active again after trauma to the skin from injury or sunburn, as was the case for this patient. Increased age, prolonged prodromal pain and severe acute pain are risk factors for severe post-herpetic neuralgia.5,6 Zosteriform herpes simplex may mimic herpes zoster. Primary varicella, disseminated herpes zoster, disseminated herpes simplex, and other blistering diseases of viral, bacterial or autoimmune etiologies might also be confused with herpes zoster. The Center for Disease Control and Prevention’s Web site (www.cdc.gov) has more information.7, 8 About 20% of adults exposed to the varicella virus during childhood will suffer a recurrence of herpes zoster.10 Remember, VZV can be transmitted to individuals with no prior history of varicella or shingles. Therefore, close contact with active lesions should be avoided. Laboratory Diagnosis In this patient, the diagnosis of HZO was made on clinical bases and was confirmed with polymerase chain reaction (PCR) for VZV DNA. The characteristic cytologic changes and multinucleate giant cells induced by VZV can be seen in Tzanck smears. Punch biopsy provides more reliable material for histological examination. These two laboratory studies don’t distinguish herpes simplex viruses (HSV-1 and HSV-2), and VZV. VZV infection is confirmed by isolation of virus in tissue culture, which often is positive within 48 hours of inoculation, but may take up to 5 days. PCR is growing in uses and availability. It’s a rapid, sensitive, and simple method for diagnosis of VZV. A PCR assay configured to detect vaccinia is under evaluation. Direct fluorescent antibody testing is preferred to a viral culture. It’s also a rapid test, it types the virus, and has a higher yield than a culture will produce. Electron microscopy of lesion material can be useful in differentiating herpes viruses from poxviruses such as vaccinia, but a limited number of centers have this capability. Vaccinia can be readily grown in routine cell culture and identified by referral to a specialty laboratory. Complications of HZO Post-herpetic complications are more common in HZO than in other forms of zoster. Eye involvement poses a risk to vision in the absence of prompt detection and treatment. Iritis, iridocyclitis, secondary glaucoma from uveitis or steroid treatment, keratitis, corneal neovascularization, corneal tissue ulcerations, scarring, and secondary bacterial or fungal infection are possible. In addition, palsy of the third cranial nerve and occasionally of the fourth and sixth cranial nerves may occur.2,9,10 Post-herpetic neuralgia is observed in more than 50% of patients with HZO and can be severe and long lasting; this requires aggressive management.1 Treatment HZO requires aggressive treatment and follow-up monitoring. Obtain ophthalmologic consultation early if the patient has significant ocular symptoms. Local treatment modalities may include warm and moist compresses and ocular lubricants to promote hydration of the cornea and conjunctivae. In addition, capsaicin cream can deplete pain fibers of substance P and reduce pain impulses. Patients must apply this cream regularly four times a day after their lesions have developed a crust, and they should avoid contact with their eyes. Antiviral agents are the cornerstone of systemic treatment of HZO and should be started within 72 hours of onset. Here’s a look at the most common antivirals used to treat HZO, and other typical treatments: Acyclovir (Zovirax). This drug shortens duration of lesions, reduces pain, and leads to faster resolution of lesions. It aborts recurrences if immediately initiated when symptoms surface. The recommended dose for HZO is 800 mg PO five times per day for 7 to 10 days. Valacyclovir (Valtrex). A prodrug, Valtrex rapidly converts to acyclovir. Although more expensive, this drug has a more convenient dosing regimen than acyclovir. It’s given 1000 mg PO t.i.d. for 7 days. Valacyclovir is as effective as acyclovir in preventing ocular complications of HZO, including conjunctivitis, keratitis and pain. Tolerability of both drugs is similar.11,12 Famciclovir (Famvir). Also a prodrug, Famvir is biotransformed into active metabolite penciclovir. The recommended dose for adults is 500 mg PO t.i.d. for 7 days. Famciclovir treatment is comparable to valacyclovir treatment in speeding the resolution of zoster-associated pain and post-herpetic neuralgia, but current wholesale prices indicate that valacyclovir is more cost-effective.12 Systemic corticosteroids are used to decrease pain levels. Use prednisone at 1 to 2 mg/kg PO qd, (not to exceed 60 mg/dl), then taper over 2 weeks as symptoms resolve. Tricyclic antidepressants (for example, amitriptyline [Elavil]). These drugs are often helpful in treating post-herpetic neuralgia. Administer them early in the course of HZO. Analgesics (narcotic agents, acetaminophen, aspirin, or NSAIDs) may also be used. Administer antibiotics that will treat Gram-positive skin flora if you detect a secondary bacterial infection of the vesicles. According to available evidence in patients older than 50 years, antiviral therapy (famciclovir or valacyclovir for 7 days) started within 72 hours of rash onset and/or low-dose amitriptyline (for 90 days) may be offered to reduce the incidence and duration of post-herpetic neuralgia.10,11,12 Our patient was treated with valacyclovir 100 mg PO t.i.d.. Seven days later the pain subsided, and a crust formed on her forehead, replacing previous vesicles. She also didn’t develop any post-herpetic neuralgia. Do you have a case you’d like to see published in this column? If so, please send a write-up (about 600 to 800 words) and an image of the patient’s condition. You may also include a follow-up image of the patient to accompany the discussion portion of the case. Please send materials to: Dr. Amor Khachemoune, Georgetown University Medical Center, Division of Dermatology, 3800 Reservoir Road, NW 5PHC, Washington, DC 20007. Or e-mail them to amorkh@pol.net.
Patient Presentation This 61-year-old patient presented with a 3-day history of vesicles and crusts on the forehead. She reports a history of a minor trauma to the forehead, which occurred several days before she developed a burning sensation and mild tenderness on her forehead, followed by the eruption of vesicles. She denied fevers, headache, backache, chills, vomiting or severe abdominal pain. She reported no ocular symptoms. Her past medical history was unremarkable. The patient wasn’t sure if she ever developed varicella during childhood, and denied having similar eruptions on any part of her body prior to this episode. Her status of immunity to the varicella couldn’t be determined. She may have been vaccinated for smallpox during childhood, but there was no recent history of revaccination. What is Your Diagnosis? Diagnosis: Herpes Zoster Ophthalmicus (HZO) HZO is defined as cutaneous lesions in the dermatome associated with the ophthalmic division of the trigeminal nerve. HZO represents reactivated varicella zoster virus (VZV), which travels down the ophthalmic nerve from the trigeminal ganglion, taking 3 to 4 days to reach the nerve endings.1,2 The ophthalmic division of the trigeminal nerve, also referred to as the first branch of the fifth cranial nerve (CN V1), has three main parts: the frontal nerve with its two main branches (supraorbital and supratrochlear), the lacrimal nerve, and the nasociliary nerve. The supraorbital and supratrochlear branches of the frontal nerve supply the upper eyelid and forehead and are most often involved in HZO. The lacrimal nerve exits the orbit laterally and supplies the lateral skin of the upper eyelids and lacrimal glands. The nasociliary nerve divides into the posterior ethmoidal, anterior ethmoidal, and infratrochlear nerves. It supplies the tip of the nose through the external nasal nerve, a branch of the anterior ethmoidal nerve and the root of the nose through the infratrochlear nerve. Watch for These Symptoms And Risk Factors Paresthesias or pain along the involved dermatome may precede the development of the vesicles. Cutaneous vesicular eruption over the forehead, lymph node enlargement in the drainage areas, fever, malaise, headache, sometimes neck stiffness, and a red eye follow. Don’t confuse prodromal lymphadenopathy with later reactive adenopathy caused by secondary infection of vesicles. Hutchinson’s sign refers to the presence of VZV vesicles on the side or the tip of the nose, and heralds ocular involvement. However, severe ocular complications can occur with a vesicular rash anywhere on the forehead. Risk factors for reactivation of VZV are diabetes, advancing age, cancer, surgery, radiation, chemotherapy, immune-suppressing drugs, systemic corticosteroid therapy, stress, and congenital or acquired immunosuppression.1,3 Due to the increased severity and risk of patients with HIV, a patient younger than 45 years old presenting with herpes zoster should be considered at risk for HIV.4 The virus may become active again after trauma to the skin from injury or sunburn, as was the case for this patient. Increased age, prolonged prodromal pain and severe acute pain are risk factors for severe post-herpetic neuralgia.5,6 Zosteriform herpes simplex may mimic herpes zoster. Primary varicella, disseminated herpes zoster, disseminated herpes simplex, and other blistering diseases of viral, bacterial or autoimmune etiologies might also be confused with herpes zoster. The Center for Disease Control and Prevention’s Web site (www.cdc.gov) has more information.7, 8 About 20% of adults exposed to the varicella virus during childhood will suffer a recurrence of herpes zoster.10 Remember, VZV can be transmitted to individuals with no prior history of varicella or shingles. Therefore, close contact with active lesions should be avoided. Laboratory Diagnosis In this patient, the diagnosis of HZO was made on clinical bases and was confirmed with polymerase chain reaction (PCR) for VZV DNA. The characteristic cytologic changes and multinucleate giant cells induced by VZV can be seen in Tzanck smears. Punch biopsy provides more reliable material for histological examination. These two laboratory studies don’t distinguish herpes simplex viruses (HSV-1 and HSV-2), and VZV. VZV infection is confirmed by isolation of virus in tissue culture, which often is positive within 48 hours of inoculation, but may take up to 5 days. PCR is growing in uses and availability. It’s a rapid, sensitive, and simple method for diagnosis of VZV. A PCR assay configured to detect vaccinia is under evaluation. Direct fluorescent antibody testing is preferred to a viral culture. It’s also a rapid test, it types the virus, and has a higher yield than a culture will produce. Electron microscopy of lesion material can be useful in differentiating herpes viruses from poxviruses such as vaccinia, but a limited number of centers have this capability. Vaccinia can be readily grown in routine cell culture and identified by referral to a specialty laboratory. Complications of HZO Post-herpetic complications are more common in HZO than in other forms of zoster. Eye involvement poses a risk to vision in the absence of prompt detection and treatment. Iritis, iridocyclitis, secondary glaucoma from uveitis or steroid treatment, keratitis, corneal neovascularization, corneal tissue ulcerations, scarring, and secondary bacterial or fungal infection are possible. In addition, palsy of the third cranial nerve and occasionally of the fourth and sixth cranial nerves may occur.2,9,10 Post-herpetic neuralgia is observed in more than 50% of patients with HZO and can be severe and long lasting; this requires aggressive management.1 Treatment HZO requires aggressive treatment and follow-up monitoring. Obtain ophthalmologic consultation early if the patient has significant ocular symptoms. Local treatment modalities may include warm and moist compresses and ocular lubricants to promote hydration of the cornea and conjunctivae. In addition, capsaicin cream can deplete pain fibers of substance P and reduce pain impulses. Patients must apply this cream regularly four times a day after their lesions have developed a crust, and they should avoid contact with their eyes. Antiviral agents are the cornerstone of systemic treatment of HZO and should be started within 72 hours of onset. Here’s a look at the most common antivirals used to treat HZO, and other typical treatments: Acyclovir (Zovirax). This drug shortens duration of lesions, reduces pain, and leads to faster resolution of lesions. It aborts recurrences if immediately initiated when symptoms surface. The recommended dose for HZO is 800 mg PO five times per day for 7 to 10 days. Valacyclovir (Valtrex). A prodrug, Valtrex rapidly converts to acyclovir. Although more expensive, this drug has a more convenient dosing regimen than acyclovir. It’s given 1000 mg PO t.i.d. for 7 days. Valacyclovir is as effective as acyclovir in preventing ocular complications of HZO, including conjunctivitis, keratitis and pain. Tolerability of both drugs is similar.11,12 Famciclovir (Famvir). Also a prodrug, Famvir is biotransformed into active metabolite penciclovir. The recommended dose for adults is 500 mg PO t.i.d. for 7 days. Famciclovir treatment is comparable to valacyclovir treatment in speeding the resolution of zoster-associated pain and post-herpetic neuralgia, but current wholesale prices indicate that valacyclovir is more cost-effective.12 Systemic corticosteroids are used to decrease pain levels. Use prednisone at 1 to 2 mg/kg PO qd, (not to exceed 60 mg/dl), then taper over 2 weeks as symptoms resolve. Tricyclic antidepressants (for example, amitriptyline [Elavil]). These drugs are often helpful in treating post-herpetic neuralgia. Administer them early in the course of HZO. Analgesics (narcotic agents, acetaminophen, aspirin, or NSAIDs) may also be used. Administer antibiotics that will treat Gram-positive skin flora if you detect a secondary bacterial infection of the vesicles. According to available evidence in patients older than 50 years, antiviral therapy (famciclovir or valacyclovir for 7 days) started within 72 hours of rash onset and/or low-dose amitriptyline (for 90 days) may be offered to reduce the incidence and duration of post-herpetic neuralgia.10,11,12 Our patient was treated with valacyclovir 100 mg PO t.i.d.. Seven days later the pain subsided, and a crust formed on her forehead, replacing previous vesicles. She also didn’t develop any post-herpetic neuralgia. Do you have a case you’d like to see published in this column? If so, please send a write-up (about 600 to 800 words) and an image of the patient’s condition. You may also include a follow-up image of the patient to accompany the discussion portion of the case. Please send materials to: Dr. Amor Khachemoune, Georgetown University Medical Center, Division of Dermatology, 3800 Reservoir Road, NW 5PHC, Washington, DC 20007. Or e-mail them to amorkh@pol.net.
