W e’ve seen an alarming increase in the incidence of Gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Pneumococci in our elderly patients. While vancomycin (Vancocin) has been considered the drug of last defense against Gram-positive multidrug-resistant bacteria, the late 1980’s saw a rise in vancomycin-resistant bacteria, including vancomycin-resistant Enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated.1 Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including post-surgical wound infections, severe carbunculosis and erysipelas. With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid (Zyvox) and quinupristin/dalfopristin (Synercid). Treating bacterial skin and skin structure infections in elderly patients is crucial — here, we’ll discuss new therapeutic options and then review treatments for some of the most common infections we see, like herpes zoster and onychomycosis. New Therapies for Cutaneous Infections Linezolid is an oxazolidinone antibiotic, shown to be effective for nosocomial and community-acquired pneumonias, vancomycin-resistant Enterococcus faecium (VREF) infections, and skin infections due to certain Staphylococcus or Streptococcus species.40 The oxazolidinones are a novel class of antibiotics first discovered in 1987.41 They are the first new antibiotics to have been discovered in the past 35 years. Currently linezolid is FDA-approved for the treatment of various Gram-positive infections, including both nosocomial and community-acquired pneumonias, complicated and uncomplicated skin and skin structure infections, and vancomycin-resistant Enterococcus infections. The recommended dosage of linezolid depends on the severity of the skin or soft tissue infection. The recommended dosage for uncomplicated infections is 400-mg every 12 hours for 10 to 14 days. For complicated infections, 600-mg twice daily either via intravenous infusion or orally is recommended. Because the absolute bioavailability after oral dosing is nearly 100%, no dosage changes are needed when switching from intravenous to oral therapy.42 Quinupristin/dalfopristin (Synercid, 30:70 ratio) is a combination of two semisynthetic pristinamycin derivatives and is the first parenteral streptogramin antibacterial agent. Both quinupristin and dalfopristin have antibacterial capability individually, but demonstrate synergistic activity when used in combination. Much of the clinical experience with this antibiotic is derived from five comparative trials and an FDA-sanctioned emergency-use program for patients without alternative therapies. FDA indications for quinupristin/dalfopristin are serious infections associated with VREF bacteremia and complicated skin and skin structure infections caused by methicillin-sensitive S. aureus or S. pyogenes. VREF infections are difficult to treat and few therapeutic options are currently available. These pathogens are resistant to most beta-lactam and aminoglycoside antibiotics. For complicated skin or skin structure infections, the recommended dose is 7.5 mg/kg intravenously twice daily for at least 7 days. The drug can be administered up to three times daily for bacteremic patients. Dose adjustment to 5 mg/kg is recommended for patients with hepatic insufficiency. No dose adjustment is needed for elderly or renally impaired patients. Treating Herpes Zoster Herpes zoster, which is caused by reactivation in adults of the varicella-zoster virus (VZV) that causes chicken pox in children, is primarily seen in older adults. After acute varicella infection, VZV becomes latent in the dorsal root ganglia. An unknown triggering mechanism, possibly caused by declining or impaired cell-mediated immunity, results in a reactivation of VZV. Infection involves the ganglia and satellite cells of the affected region. In immunocompetent persons, herpes zoster is usually confined to a single dermatome. Cutaneous or visceral dissemination of herpes zoster in immunocompetent individuals is rare. Herpes zoster is also associated with a characteristic pain syndrome. The infected, inflamed, and damaged nerve is the source of the acute and chronic pain of herpes zoster. Pain associated with zoster can be divided into the following three types.1 1. Prodromal pain is a sharp stabbing pain that occurs before the onset of rash. Depending on the affected dermatome, prodromal pain may be misdiagnosed as myocardial infarction, appendicitis, or a gallbladder or kidney stone attack. 2. Acute pain is often classified as lasting throughout the course of the vesicular eruption. 3. Chronic pain, also known as post-herpes zoster pain or postherpetic neuralgia (PHN), can last from months to years after the disappearance of the herpes zoster lesion. (See Postherpetic Neuralgia on page 57 for more details on this complication.) Antiviral Therapy Antiviral therapy is a first-line therapy for herpes zoster. Antiviral therapy is aimed at decreasing viral replication, thereby lessening nerve damage or inflammation, and reducing the duration and severity of long-term pain syndromes. The benefits of antiviral therapy in reducing the extent and duration of pain have been seen primarily in patients older than 50, reflecting the age-related association of long-term pain.1 Regardless of age, consider early antiviral therapy for any patient who has prodromal pain, and early moderate or severe pain, as well as for patients with known or suspected immunocompromised systems. To be effective, antiviral therapy must be instituted early, usually within 72 hours of the onset of the rash. Antiviral therapy may be of benefit after 72 hours in patients who are at high risk of PHN, in whom there is evidence of viral replication. After 72 hours, we strongly encourage antiviral therapy for any immunocompromised patient who still has vesicles —or an increasing number of vesicles.1 For many years, acyclovir (Zovirax) was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Institute acyclovir within 72 hours of onset of the rash at 800 mg five times per day for 7 days. If the herpes zoster patients is infected with HIV, continue therapy until new lesions stop forming, and those that have formed crust over. Failure to maintain an adequate antiviral regimen in this population may lead to a clinical entity known as verrucous zoster. These wart-like lesions continue to display ongoing viral replication and are very difficult to treat once they have developed.1 VZV is less acyclovir-sensitive than HSV, and therefore higher doses are needed for patients with VZV. It’s particularly important that elderly patients receive the full herpes zoster dose of acyclovir, because they’re at the highest risk for chronic pain. Although the proper dose of acyclovir for the treatment of patients with VZV is four times greater than the dose for the treatment of patients with HSV, serum levels are only double. Acyclovir remains one of the safest antimicrobial agents. It’s preferentially taken up by infected cells and requires activation by viral enzymes to be active. Once phosphorylated into its active moiety, acyclovir has 100 times the affinity for viral DNA polymerase than for cellular DNA polymerases. Be sure patients maintain adequate hydration because the drug is excreted via the kidneys.1 According to analysis of pooled data from various placebo-controlled trials, acyclovir has exhibited significant impact on the severity, duration and relative risk of long-term pain.2 Other Antiviral Treatments Famciclovir (Famvir), the oral form of the antiviral agent penciclovir (Denavir), is rapidly absorbed and efficiently converted in virally infected cells through phosphorylation to its active metabolite, penciclovir-triphosphate. Penciclovir-triphosphate competitively inhibits viral DNA polymerase, thereby halting DNA synthesis and viral replication.3 Valacyclovir (Valtrex) is the L-valyl ester of acyclovir. It’s converted in vivo to acyclovir and the naturally occurring amino acid valine. Valacyclovir provides three to five times the oral bioavailability of acyclovir compared with the unesterased compound. This results in acyclovir exposures similar to those seen with intravenous acyclovir.1 Other Herpes Zoster Treatments Combination therapy with a corticosteroid and an antiviral drug in patients with zoster has been evaluated in two trials. In both trials there was a definite benefit in reducing acute pain in patients receiving prednisolone plus acyclovir versus those receiving acyclovir alone or placebo. However there was no difference in postherpetic neuralgia at 6 months among the three groups.30,32 Antagonists to N-methyl-D-aspartate receptors may lessen neuropathic pain by altering abnormal central nervous system processing. The available antagonists of these receptors, such as ketamine and dextromethorphan, reduce windup and neuropathic pain but have many adverse effects.33 Cutaneous Reactions Following Herpes Zoster Infections Many cutaneous reactions are known to develop within resolved varicella-zoster lesions. These include granuloma annulare, sarcoidal granulomas, tuberculoid granulomas, lymphoma, pseudolymphoma, granulomatous vasculitis, and Kaposi’s sarcoma.36 The interval between the varicella-zoster infection and any of the above is relatively short (average 6 months; range 2 weeks to 4 years).36 Onychomycosis Another common infection seen in elderly patients is onychomycosis, which is found more often in elderly males than females.37 Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and non-dermatophyte molds.38 There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candida onychomycosis. Distal subungual onychomycosis is the most common type of onychomycosis. A whitish-brown discoloration begins at the free edge or the lateral nail fold, invades the distal nail bed, and travels proximally. Subungual hyperkeratosis may lead to separation of the nail plate from the nail bed, thus providing a conducive environment for secondary bacterial infections. Proximal subungual onychomycosis, the least common variant, presents as a whitish-brown area on the proximal part of the nail plate that eventually enlarges to affect the entire nail. White superficial onychomycosis, an infection in which the toenails, not the fingernails are affected, produces a friable, sharply delineated, white nail. Candidal onychomycosis, seen in patients with chronic mucocutaneous candidiasis, affects both fingernails and toenails. The nail bed and nail plate both thicken. The surface of the nail turns a brownish-yellow and becomes furrowed. Paronychia often develops concurrently. Before initiation of therapy, it is important to document the presence of fungi utilizing one or more diagnostic techniques, including KOH preparation, fungal culture, and nail plate biopsy with PAS (periodic acid-Schiff) stain. Proper diagnosis is necessary because other disorders can mimic onychomycosis, including psoriasis, irritant dermatitis and trauma. Perform laboratory monitoring, including liver function tests, at baseline and at variable intervals (at 4 and 8 weeks for itraconazole [Sporanox], at 6 weeks for terbinafine [Lamisil], for a 3-month courses) on patients taking either medication for more than 1 month.38 Recently, ciclopirox lacquer (Loprox, Penlac), a topical agent has been approved for the treatment of onychomycosis. Try this on patients who aren’t candidates for the other therapies — it has significantly lower efficacy than the oral medications.41 Aggressive Monitoring The diagnosis and management of diseases of the skin are significant issues in the elderly population. With advances in these areas, we have new tools to combat these diseases and limit morbidity. It is important for clinicians to aggressively monitor and treat these diseases in the elderly because of the potential for immunosuppression in this population. Further advances in therapy and the potential for the development of vaccines will aid in the therapy of these diseases.
Part 2: Diagnosing and Managing Skin Infections in the Elderly
W e’ve seen an alarming increase in the incidence of Gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Pneumococci in our elderly patients. While vancomycin (Vancocin) has been considered the drug of last defense against Gram-positive multidrug-resistant bacteria, the late 1980’s saw a rise in vancomycin-resistant bacteria, including vancomycin-resistant Enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated.1 Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including post-surgical wound infections, severe carbunculosis and erysipelas. With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid (Zyvox) and quinupristin/dalfopristin (Synercid). Treating bacterial skin and skin structure infections in elderly patients is crucial — here, we’ll discuss new therapeutic options and then review treatments for some of the most common infections we see, like herpes zoster and onychomycosis. New Therapies for Cutaneous Infections Linezolid is an oxazolidinone antibiotic, shown to be effective for nosocomial and community-acquired pneumonias, vancomycin-resistant Enterococcus faecium (VREF) infections, and skin infections due to certain Staphylococcus or Streptococcus species.40 The oxazolidinones are a novel class of antibiotics first discovered in 1987.41 They are the first new antibiotics to have been discovered in the past 35 years. Currently linezolid is FDA-approved for the treatment of various Gram-positive infections, including both nosocomial and community-acquired pneumonias, complicated and uncomplicated skin and skin structure infections, and vancomycin-resistant Enterococcus infections. The recommended dosage of linezolid depends on the severity of the skin or soft tissue infection. The recommended dosage for uncomplicated infections is 400-mg every 12 hours for 10 to 14 days. For complicated infections, 600-mg twice daily either via intravenous infusion or orally is recommended. Because the absolute bioavailability after oral dosing is nearly 100%, no dosage changes are needed when switching from intravenous to oral therapy.42 Quinupristin/dalfopristin (Synercid, 30:70 ratio) is a combination of two semisynthetic pristinamycin derivatives and is the first parenteral streptogramin antibacterial agent. Both quinupristin and dalfopristin have antibacterial capability individually, but demonstrate synergistic activity when used in combination. Much of the clinical experience with this antibiotic is derived from five comparative trials and an FDA-sanctioned emergency-use program for patients without alternative therapies. FDA indications for quinupristin/dalfopristin are serious infections associated with VREF bacteremia and complicated skin and skin structure infections caused by methicillin-sensitive S. aureus or S. pyogenes. VREF infections are difficult to treat and few therapeutic options are currently available. These pathogens are resistant to most beta-lactam and aminoglycoside antibiotics. For complicated skin or skin structure infections, the recommended dose is 7.5 mg/kg intravenously twice daily for at least 7 days. The drug can be administered up to three times daily for bacteremic patients. Dose adjustment to 5 mg/kg is recommended for patients with hepatic insufficiency. No dose adjustment is needed for elderly or renally impaired patients. Treating Herpes Zoster Herpes zoster, which is caused by reactivation in adults of the varicella-zoster virus (VZV) that causes chicken pox in children, is primarily seen in older adults. After acute varicella infection, VZV becomes latent in the dorsal root ganglia. An unknown triggering mechanism, possibly caused by declining or impaired cell-mediated immunity, results in a reactivation of VZV. Infection involves the ganglia and satellite cells of the affected region. In immunocompetent persons, herpes zoster is usually confined to a single dermatome. Cutaneous or visceral dissemination of herpes zoster in immunocompetent individuals is rare. Herpes zoster is also associated with a characteristic pain syndrome. The infected, inflamed, and damaged nerve is the source of the acute and chronic pain of herpes zoster. Pain associated with zoster can be divided into the following three types.1 1. Prodromal pain is a sharp stabbing pain that occurs before the onset of rash. Depending on the affected dermatome, prodromal pain may be misdiagnosed as myocardial infarction, appendicitis, or a gallbladder or kidney stone attack. 2. Acute pain is often classified as lasting throughout the course of the vesicular eruption. 3. Chronic pain, also known as post-herpes zoster pain or postherpetic neuralgia (PHN), can last from months to years after the disappearance of the herpes zoster lesion. (See Postherpetic Neuralgia on page 57 for more details on this complication.) Antiviral Therapy Antiviral therapy is a first-line therapy for herpes zoster. Antiviral therapy is aimed at decreasing viral replication, thereby lessening nerve damage or inflammation, and reducing the duration and severity of long-term pain syndromes. The benefits of antiviral therapy in reducing the extent and duration of pain have been seen primarily in patients older than 50, reflecting the age-related association of long-term pain.1 Regardless of age, consider early antiviral therapy for any patient who has prodromal pain, and early moderate or severe pain, as well as for patients with known or suspected immunocompromised systems. To be effective, antiviral therapy must be instituted early, usually within 72 hours of the onset of the rash. Antiviral therapy may be of benefit after 72 hours in patients who are at high risk of PHN, in whom there is evidence of viral replication. After 72 hours, we strongly encourage antiviral therapy for any immunocompromised patient who still has vesicles —or an increasing number of vesicles.1 For many years, acyclovir (Zovirax) was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Institute acyclovir within 72 hours of onset of the rash at 800 mg five times per day for 7 days. If the herpes zoster patients is infected with HIV, continue therapy until new lesions stop forming, and those that have formed crust over. Failure to maintain an adequate antiviral regimen in this population may lead to a clinical entity known as verrucous zoster. These wart-like lesions continue to display ongoing viral replication and are very difficult to treat once they have developed.1 VZV is less acyclovir-sensitive than HSV, and therefore higher doses are needed for patients with VZV. It’s particularly important that elderly patients receive the full herpes zoster dose of acyclovir, because they’re at the highest risk for chronic pain. Although the proper dose of acyclovir for the treatment of patients with VZV is four times greater than the dose for the treatment of patients with HSV, serum levels are only double. Acyclovir remains one of the safest antimicrobial agents. It’s preferentially taken up by infected cells and requires activation by viral enzymes to be active. Once phosphorylated into its active moiety, acyclovir has 100 times the affinity for viral DNA polymerase than for cellular DNA polymerases. Be sure patients maintain adequate hydration because the drug is excreted via the kidneys.1 According to analysis of pooled data from various placebo-controlled trials, acyclovir has exhibited significant impact on the severity, duration and relative risk of long-term pain.2 Other Antiviral Treatments Famciclovir (Famvir), the oral form of the antiviral agent penciclovir (Denavir), is rapidly absorbed and efficiently converted in virally infected cells through phosphorylation to its active metabolite, penciclovir-triphosphate. Penciclovir-triphosphate competitively inhibits viral DNA polymerase, thereby halting DNA synthesis and viral replication.3 Valacyclovir (Valtrex) is the L-valyl ester of acyclovir. It’s converted in vivo to acyclovir and the naturally occurring amino acid valine. Valacyclovir provides three to five times the oral bioavailability of acyclovir compared with the unesterased compound. This results in acyclovir exposures similar to those seen with intravenous acyclovir.1 Other Herpes Zoster Treatments Combination therapy with a corticosteroid and an antiviral drug in patients with zoster has been evaluated in two trials. In both trials there was a definite benefit in reducing acute pain in patients receiving prednisolone plus acyclovir versus those receiving acyclovir alone or placebo. However there was no difference in postherpetic neuralgia at 6 months among the three groups.30,32 Antagonists to N-methyl-D-aspartate receptors may lessen neuropathic pain by altering abnormal central nervous system processing. The available antagonists of these receptors, such as ketamine and dextromethorphan, reduce windup and neuropathic pain but have many adverse effects.33 Cutaneous Reactions Following Herpes Zoster Infections Many cutaneous reactions are known to develop within resolved varicella-zoster lesions. These include granuloma annulare, sarcoidal granulomas, tuberculoid granulomas, lymphoma, pseudolymphoma, granulomatous vasculitis, and Kaposi’s sarcoma.36 The interval between the varicella-zoster infection and any of the above is relatively short (average 6 months; range 2 weeks to 4 years).36 Onychomycosis Another common infection seen in elderly patients is onychomycosis, which is found more often in elderly males than females.37 Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and non-dermatophyte molds.38 There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candida onychomycosis. Distal subungual onychomycosis is the most common type of onychomycosis. A whitish-brown discoloration begins at the free edge or the lateral nail fold, invades the distal nail bed, and travels proximally. Subungual hyperkeratosis may lead to separation of the nail plate from the nail bed, thus providing a conducive environment for secondary bacterial infections. Proximal subungual onychomycosis, the least common variant, presents as a whitish-brown area on the proximal part of the nail plate that eventually enlarges to affect the entire nail. White superficial onychomycosis, an infection in which the toenails, not the fingernails are affected, produces a friable, sharply delineated, white nail. Candidal onychomycosis, seen in patients with chronic mucocutaneous candidiasis, affects both fingernails and toenails. The nail bed and nail plate both thicken. The surface of the nail turns a brownish-yellow and becomes furrowed. Paronychia often develops concurrently. Before initiation of therapy, it is important to document the presence of fungi utilizing one or more diagnostic techniques, including KOH preparation, fungal culture, and nail plate biopsy with PAS (periodic acid-Schiff) stain. Proper diagnosis is necessary because other disorders can mimic onychomycosis, including psoriasis, irritant dermatitis and trauma. Perform laboratory monitoring, including liver function tests, at baseline and at variable intervals (at 4 and 8 weeks for itraconazole [Sporanox], at 6 weeks for terbinafine [Lamisil], for a 3-month courses) on patients taking either medication for more than 1 month.38 Recently, ciclopirox lacquer (Loprox, Penlac), a topical agent has been approved for the treatment of onychomycosis. Try this on patients who aren’t candidates for the other therapies — it has significantly lower efficacy than the oral medications.41 Aggressive Monitoring The diagnosis and management of diseases of the skin are significant issues in the elderly population. With advances in these areas, we have new tools to combat these diseases and limit morbidity. It is important for clinicians to aggressively monitor and treat these diseases in the elderly because of the potential for immunosuppression in this population. Further advances in therapy and the potential for the development of vaccines will aid in the therapy of these diseases.
W e’ve seen an alarming increase in the incidence of Gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Pneumococci in our elderly patients. While vancomycin (Vancocin) has been considered the drug of last defense against Gram-positive multidrug-resistant bacteria, the late 1980’s saw a rise in vancomycin-resistant bacteria, including vancomycin-resistant Enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated.1 Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including post-surgical wound infections, severe carbunculosis and erysipelas. With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid (Zyvox) and quinupristin/dalfopristin (Synercid). Treating bacterial skin and skin structure infections in elderly patients is crucial — here, we’ll discuss new therapeutic options and then review treatments for some of the most common infections we see, like herpes zoster and onychomycosis. New Therapies for Cutaneous Infections Linezolid is an oxazolidinone antibiotic, shown to be effective for nosocomial and community-acquired pneumonias, vancomycin-resistant Enterococcus faecium (VREF) infections, and skin infections due to certain Staphylococcus or Streptococcus species.40 The oxazolidinones are a novel class of antibiotics first discovered in 1987.41 They are the first new antibiotics to have been discovered in the past 35 years. Currently linezolid is FDA-approved for the treatment of various Gram-positive infections, including both nosocomial and community-acquired pneumonias, complicated and uncomplicated skin and skin structure infections, and vancomycin-resistant Enterococcus infections. The recommended dosage of linezolid depends on the severity of the skin or soft tissue infection. The recommended dosage for uncomplicated infections is 400-mg every 12 hours for 10 to 14 days. For complicated infections, 600-mg twice daily either via intravenous infusion or orally is recommended. Because the absolute bioavailability after oral dosing is nearly 100%, no dosage changes are needed when switching from intravenous to oral therapy.42 Quinupristin/dalfopristin (Synercid, 30:70 ratio) is a combination of two semisynthetic pristinamycin derivatives and is the first parenteral streptogramin antibacterial agent. Both quinupristin and dalfopristin have antibacterial capability individually, but demonstrate synergistic activity when used in combination. Much of the clinical experience with this antibiotic is derived from five comparative trials and an FDA-sanctioned emergency-use program for patients without alternative therapies. FDA indications for quinupristin/dalfopristin are serious infections associated with VREF bacteremia and complicated skin and skin structure infections caused by methicillin-sensitive S. aureus or S. pyogenes. VREF infections are difficult to treat and few therapeutic options are currently available. These pathogens are resistant to most beta-lactam and aminoglycoside antibiotics. For complicated skin or skin structure infections, the recommended dose is 7.5 mg/kg intravenously twice daily for at least 7 days. The drug can be administered up to three times daily for bacteremic patients. Dose adjustment to 5 mg/kg is recommended for patients with hepatic insufficiency. No dose adjustment is needed for elderly or renally impaired patients. Treating Herpes Zoster Herpes zoster, which is caused by reactivation in adults of the varicella-zoster virus (VZV) that causes chicken pox in children, is primarily seen in older adults. After acute varicella infection, VZV becomes latent in the dorsal root ganglia. An unknown triggering mechanism, possibly caused by declining or impaired cell-mediated immunity, results in a reactivation of VZV. Infection involves the ganglia and satellite cells of the affected region. In immunocompetent persons, herpes zoster is usually confined to a single dermatome. Cutaneous or visceral dissemination of herpes zoster in immunocompetent individuals is rare. Herpes zoster is also associated with a characteristic pain syndrome. The infected, inflamed, and damaged nerve is the source of the acute and chronic pain of herpes zoster. Pain associated with zoster can be divided into the following three types.1 1. Prodromal pain is a sharp stabbing pain that occurs before the onset of rash. Depending on the affected dermatome, prodromal pain may be misdiagnosed as myocardial infarction, appendicitis, or a gallbladder or kidney stone attack. 2. Acute pain is often classified as lasting throughout the course of the vesicular eruption. 3. Chronic pain, also known as post-herpes zoster pain or postherpetic neuralgia (PHN), can last from months to years after the disappearance of the herpes zoster lesion. (See Postherpetic Neuralgia on page 57 for more details on this complication.) Antiviral Therapy Antiviral therapy is a first-line therapy for herpes zoster. Antiviral therapy is aimed at decreasing viral replication, thereby lessening nerve damage or inflammation, and reducing the duration and severity of long-term pain syndromes. The benefits of antiviral therapy in reducing the extent and duration of pain have been seen primarily in patients older than 50, reflecting the age-related association of long-term pain.1 Regardless of age, consider early antiviral therapy for any patient who has prodromal pain, and early moderate or severe pain, as well as for patients with known or suspected immunocompromised systems. To be effective, antiviral therapy must be instituted early, usually within 72 hours of the onset of the rash. Antiviral therapy may be of benefit after 72 hours in patients who are at high risk of PHN, in whom there is evidence of viral replication. After 72 hours, we strongly encourage antiviral therapy for any immunocompromised patient who still has vesicles —or an increasing number of vesicles.1 For many years, acyclovir (Zovirax) was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Institute acyclovir within 72 hours of onset of the rash at 800 mg five times per day for 7 days. If the herpes zoster patients is infected with HIV, continue therapy until new lesions stop forming, and those that have formed crust over. Failure to maintain an adequate antiviral regimen in this population may lead to a clinical entity known as verrucous zoster. These wart-like lesions continue to display ongoing viral replication and are very difficult to treat once they have developed.1 VZV is less acyclovir-sensitive than HSV, and therefore higher doses are needed for patients with VZV. It’s particularly important that elderly patients receive the full herpes zoster dose of acyclovir, because they’re at the highest risk for chronic pain. Although the proper dose of acyclovir for the treatment of patients with VZV is four times greater than the dose for the treatment of patients with HSV, serum levels are only double. Acyclovir remains one of the safest antimicrobial agents. It’s preferentially taken up by infected cells and requires activation by viral enzymes to be active. Once phosphorylated into its active moiety, acyclovir has 100 times the affinity for viral DNA polymerase than for cellular DNA polymerases. Be sure patients maintain adequate hydration because the drug is excreted via the kidneys.1 According to analysis of pooled data from various placebo-controlled trials, acyclovir has exhibited significant impact on the severity, duration and relative risk of long-term pain.2 Other Antiviral Treatments Famciclovir (Famvir), the oral form of the antiviral agent penciclovir (Denavir), is rapidly absorbed and efficiently converted in virally infected cells through phosphorylation to its active metabolite, penciclovir-triphosphate. Penciclovir-triphosphate competitively inhibits viral DNA polymerase, thereby halting DNA synthesis and viral replication.3 Valacyclovir (Valtrex) is the L-valyl ester of acyclovir. It’s converted in vivo to acyclovir and the naturally occurring amino acid valine. Valacyclovir provides three to five times the oral bioavailability of acyclovir compared with the unesterased compound. This results in acyclovir exposures similar to those seen with intravenous acyclovir.1 Other Herpes Zoster Treatments Combination therapy with a corticosteroid and an antiviral drug in patients with zoster has been evaluated in two trials. In both trials there was a definite benefit in reducing acute pain in patients receiving prednisolone plus acyclovir versus those receiving acyclovir alone or placebo. However there was no difference in postherpetic neuralgia at 6 months among the three groups.30,32 Antagonists to N-methyl-D-aspartate receptors may lessen neuropathic pain by altering abnormal central nervous system processing. The available antagonists of these receptors, such as ketamine and dextromethorphan, reduce windup and neuropathic pain but have many adverse effects.33 Cutaneous Reactions Following Herpes Zoster Infections Many cutaneous reactions are known to develop within resolved varicella-zoster lesions. These include granuloma annulare, sarcoidal granulomas, tuberculoid granulomas, lymphoma, pseudolymphoma, granulomatous vasculitis, and Kaposi’s sarcoma.36 The interval between the varicella-zoster infection and any of the above is relatively short (average 6 months; range 2 weeks to 4 years).36 Onychomycosis Another common infection seen in elderly patients is onychomycosis, which is found more often in elderly males than females.37 Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and non-dermatophyte molds.38 There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candida onychomycosis. Distal subungual onychomycosis is the most common type of onychomycosis. A whitish-brown discoloration begins at the free edge or the lateral nail fold, invades the distal nail bed, and travels proximally. Subungual hyperkeratosis may lead to separation of the nail plate from the nail bed, thus providing a conducive environment for secondary bacterial infections. Proximal subungual onychomycosis, the least common variant, presents as a whitish-brown area on the proximal part of the nail plate that eventually enlarges to affect the entire nail. White superficial onychomycosis, an infection in which the toenails, not the fingernails are affected, produces a friable, sharply delineated, white nail. Candidal onychomycosis, seen in patients with chronic mucocutaneous candidiasis, affects both fingernails and toenails. The nail bed and nail plate both thicken. The surface of the nail turns a brownish-yellow and becomes furrowed. Paronychia often develops concurrently. Before initiation of therapy, it is important to document the presence of fungi utilizing one or more diagnostic techniques, including KOH preparation, fungal culture, and nail plate biopsy with PAS (periodic acid-Schiff) stain. Proper diagnosis is necessary because other disorders can mimic onychomycosis, including psoriasis, irritant dermatitis and trauma. Perform laboratory monitoring, including liver function tests, at baseline and at variable intervals (at 4 and 8 weeks for itraconazole [Sporanox], at 6 weeks for terbinafine [Lamisil], for a 3-month courses) on patients taking either medication for more than 1 month.38 Recently, ciclopirox lacquer (Loprox, Penlac), a topical agent has been approved for the treatment of onychomycosis. Try this on patients who aren’t candidates for the other therapies — it has significantly lower efficacy than the oral medications.41 Aggressive Monitoring The diagnosis and management of diseases of the skin are significant issues in the elderly population. With advances in these areas, we have new tools to combat these diseases and limit morbidity. It is important for clinicians to aggressively monitor and treat these diseases in the elderly because of the potential for immunosuppression in this population. Further advances in therapy and the potential for the development of vaccines will aid in the therapy of these diseases.
