Shingles and Interventional Pain Treatment
Abstract: Acute shingles patients rarely come to the attention of the pain physician; instead, it is only after the lesions have healed that patients are referred to pain management. Unfortunately, by that time there is very little that can be done. Aggressive education is necessary to convince family doctors and patients that early interventional treatment by a pain physician can provide excellent pain relief as well as decrease the risk of postherpetic neuralgia – the leading cause of suicide in pain patients over 70 years old. Key words: Shingles Postherpetic
Introduction: Shingles and post herpetic neuralgia (PHN) are becoming a larger health issue as our population ages, influencing health care dollars and quality of life. Patients and health care providers have been told that the condition is untreatable, but that the pain usually goes away in time. Unfortunately, post herpetic neuralgia (the nerve pain after shingles), is a debilitating pain that may last up to a year in 50% of patients, and may even last up to a lifetime. The good news is that aggressive interventional pain management is both cost effective and efficacious in treating shingles and preventing PHN. History: Herpes zoster, or shingles, has been plaguing man since ancient times. In his book, Shingles And PHN, Thomas Carl Thomsen (1) references an essay in the History of Medicine, which stated that " 'Job was afflicted with a general eruption of sores, causing great itching, severe pain, and discoloration of skin, and tending to cause swelling of the eyelids and closure of the eyes.' A pretty good description of.shingles affecting the (eye)." The family of herpes viruses gets its name from the Greek herpetum for “creeping skin disease.” Varicella is a Latin word meaning "little pox" to distinguish the chickenpox
virus from smallpox, the highly contagious and often fatal scourge that disfigured or killed millions of people. Zoster is the Greek word for "girdle"; shingles often produces a girdle of blisters or lesions around the waist. Shingles derives its name from the Latin cingulum, which also means girdle or belt. In Italy, shingles is called St. Anthony's fire. Herpes varicella and herpes zoster were initially felt to be two different diseases, but as early as 1909 a German scientist suspected that the viruses causing chickenpox and shingles were one and the same. In the 1920's and 1930's the case was strengthened by an experiment where children were inoculated with fluid from the lesions of patients with shingles. Within 2 weeks about half the children came down with chickenpox. Finally, in 1958, detailed analyses of the viruses taken from patients with either chickenpox or shingles confirmed that the viruses were identical. The virus is now often called herpes varicella-zoster or HVZ. Incidence: The primary infection with HVZ causes chickenpox. It has been estimated that 90% of US children have contracted chickenpox by the age of 15. Approximately 1 in 10 individuals who have had chickenpox will develop shingles. Shingles strikes an estimated 200,000 (2) to 800,000 U.S. patients each year, mostly among the elderly or immunosuppressed (3). The incidence of herpes zoster infection is estimated to be as high as 4.8 cases per 1000 persons each year (2). The disease is rare in young healthy adults, but occurs in 5.1 of each 1,000 patients over age 50 and in 10.1 per 1,000 patients in their 80s. Incidence of Shingles incidence
The incidence increases with age and is higher in immunosuppressed patients or patients with cancer (4). Shingles also may be an early signal of HIV infection, especially when it occurs in a younger person (5). The incidence of herpes zoster has increased over the past several decades (6), and population studies project that 22% of Americans will be 65 or older by the year 2030 with the number of people over the age of 85 soaring to 8 million. The lifetime incidence of shingles may be 10% to 20% in the general population, and up to 50% in a cohort surviving to age 85.
Pathophysiology: HVZ is a human alpha herpes virus and looks as though a mathematician designed it. It is a microscopic sphere encasing a 20-sided geometric figure called an icosahedron. Inside the icosahedron is the genetic material of the virus, deoxyribonucleic acid (DNA). When activated, the virus reproduces inside the nucleus of an infected cell. It acquires its spherical wrapping as it buds through the nuclear membrane. The clinical infection of chickenpox has a usual course of about two weeks. After the infection, nerve terminals each receive an aliquot of defective virus particles, which cause no injury to the sensory nerves up which they travel to become latent in the first nucleate cells they encounter. Therefore, the latent virus is found in the neurons and supporting cells of the sensory ganglia, where they exist for the remainder of the host’s life. For whatever reason (senility of the body’s antibodies, infection that distracts the body’s immune system, immunocompromise, stress), the virus can “break out of prison”, “raping and pillaging” along the path of the nerve in which it was living. Strauss (7) has likened this eruption to "varicella within a single dermatome." The body’s response (like any good general) appears to be to cut off the “supply lines”, which in this case is the blood flow to the nerve itself. Ischemia of the nerve leads to death of the large myelinated or modulator nerves, leaving the small unmyelinated pain nerves unopposed. This has been confirmed by biopsy and autopsy studies (8). Clinical course: Sub clinical presentations of herpes zoster have been reported where herpes zoster had migrated to the CNS in immunocompetent patients without symptoms of CNS infection. However, for most patients, the initial presentation is of pain in a dermatomal pattern. At this time, rising titers of virus can begin to be detected. The body’s response to this invader is the initiation of the sympathetic system response, with ischemia of the nerve. Forty percent of patients experience pain more than 4 days prior to the skin eruption and 35% experience it less than 48 hours prior to the development of the rash (9). In some cases, the pain starts more than 100 days before the rash and is referred to as "preherpetic neuralgia" (10). Pruritus, paresthesias, fever, malaise and myalgia may accompany the pain of preherpetic neuralgia. In the prelesion phase, the differential diagnosis for the pain may be quite long. Trigeminal distribution might mimic subarachnoid hemorrhage or migraine headache, upper extremity lesions may look like a cervical disc pathology, while thoracic ischemia may be mistaken for cardiac pathology, costochondritis, pleurisy, or rib fracture. Abdominal pain can lead to workup for cholecystectomy, appendicitis, or peritonitis, while lower extremity shingles can look like a sciatica, or radiculitis before the lesions appear. When the rash appears, initially there may be erythema and then papules, vesicles, blebs, pustules, and then crusting. In severe cases, the lesions may coalesce to cover the entire dermatome. The crusts usually fall off by the 5th week, leaving pink scars that become hypoesthetic and hypopigmented. The most common dermatome affected is the thoracic (55% of cases), followed by the cranial (trigeminal; 15% of cases), the lumbar (14% of cases), and sacral (3% of cases) (11). While a few patients do not report pain with shingles, they are the exception. Most patients describe the pain as debilitating.
There is a condition known as zoster sine herpete, which is a dermatomal pain without a visual rash due to reactivation of the varicella zoster virus. This condition can be associated with segmental pain and motor deficits, and is diagnosed by viral analysis. However, since the varicella zoster virus can affect all levels of the nervous system in the absence of skin lesions, reactivation of the virus without rash encompasses a much broader syndrome complex than localised pain, and may be much harder to diagnose. Although the virus is presumed to hide in the nervous system between bouts of chickenpox and shingles, it has never been recovered from nerve cells at autopsies unless the patient had shingles at the time of death. In contrast, herpes simplex, which causes recurrent infections of cold sores and fever blisters, has been identified in spinal nerve cells during its latent periods. Neurologic sequelae: Motor deficits can occur in the intercostal and abdominal muscles. Trigeminal nerve involvement may result in ptosis, and the Hunt-Ramsey syndrome (involvement of the ear) may cause facial nerve paralysis. Occasionally, the rash will appear as a single spot or cluster of spots on the tip of the nose, called Hutchinson's sign. This may herald involvement of the ophthalmic nerve, which may lead to temporary or permanent blindness. Central nervous system complications include meningitis, encephalitis, mellitus and cerebral angiitis (12). Postherpetic Neuralgia 20 to 30% of shingles patients continue to have pain after the shingles lesions have healed, which is called post herpetic neuralgia (PHN). The risk increases with age, approaching 75% of patients over 70 years old. Although the mechanism of pain is not clear, ischemia of the nerve would explain the prelesion pain and the subsequent hypoesthesias. Nerve biopsies of post herpetic nerves show a loss of large myelinated “modulator” nerves, and a proliferation of unmeylinated pain nerves. It is important to note that the elderly are at higher risk for this ischemia due to peripheral vascular deterioration and fewer large fibers to begin with, and therefore would be expected to be more susceptible to the pain of post herpetic neuralgia. The natural history of PHN is not clear, but 50% of patients with PHN may continue to have pain after three months, and although 80% have resolution within 5 years, 2% have pain for more than 5 years (13). Many of these patients are refractory to treatment, and may get worse instead of better over time. In addition, some patients have pain-free intervals of weeks to months, only to have the pain reoccur (14). PHN may profoundly affect a patient’s life and functional status, leading to anorexia, depression, and interference with activities of daily living such as bathing and mobility (15). It has been described as one of the most common causes of pain in the elderly and the leading cause of suicide in chronic pain patients over the age of 70 (16). Watson estimates that "despite all . . . measures, at least 30% of patients with PHN remain either completely refractory or unsatisfactorily relieved by the best we have to offer, and new approaches to this vexing problem are sorely needed." (17) Treatment approach for shingles: The goal of treatment is to treat the pain of the acute disease and prevent the occurrence of post herpetic neuralgia. The earlier a patient is treated, the less likely the condition will
progress to PHN. Some physicians only send the patient for treatment after the lesions have healed. This is a great disservice to the patients, allowing needless pain and suffering. Because it is impossible to accurately predict which patients will progress to PHN, it is our suggestion that all patients be considered for treatment. The incidence of PHN goes up dramatically with age, and the length of time with pain also goes up. Up to 50% of patients over 70 year old with shingles will still have pain after more than one year.
Antivirals have been advocated since the late 1970’s, initially with encouraging results. If begun within 72 hours after the appearance of the rash, famciclovir, valacyclovir or acyclovir reduce acute pain in immunocompetent patients with zoster. However, the long-term results have been less impressive, and a survey of the incidence of PHN in 1992 was not significantly changed since the 1940’s, suggesting that the antivirals did not change the risk of subsequent PHN (18). Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids do not significantly affect the prevalence of PHN (19). In a study of 600 adults over the age of 50 with early shingles (less than 7 days after the rash occurred) patients were randomized to receive either IV acyclovir with prednisone or epidural local anesthetic and steroids. At one year, 22% of the acyclovir patients still had pain, while only 1% of the epidural patients still had pain (20).
The interventional approach to the treatment of shingles can be traced to as early as 1969, when Colding described the use of regional sympathetic blocks (21) for zoster treatment. Sympathetic blocks can be used to prevent the vasoconstriction thought to cause the pain and nerve damage. Winnie (22) described that the incidence of success is a function of the rapidity of treatment. Virtually 100% success was obtained if the injections were done within 1-2 weeks after the onset of the lesions. After 4-6 weeks, the success rate falls to 20%, and continues to fall with time (23). Bonica felt so strongly about the effectiveness of interventional treatment that he said "I am so convinced of the efficacy of the procedure that I have had neural blockade as the sole treatment for my own case of HZ and for that of my wife and one of my siblings." (24) Case histories CASE I A 55 year-old male presented to our clinic with complaints of left shoulder pain and rash for a week. Pain was gradually getting worse despite oxycodone, prednisone, and acyclovir. He was noted to have a vesicular rash along a T11 dermatome. Patient had a history of atrial fibrillation and was on coumadin. He was treated with one paravertebral nerve block and topical ketoprofen/lidocaine. One week later he returned and noted 100% pain relief CASE II A 70 year old male presented to the ER with a history of a severe vertex headache for several days. He was diagnosed as having a “migraine” (despite a negative history of similar headaches in the past) and was given oxycodone. Two days later, skin lesions appeared over his right eyebrow and forehead. He went to his internist who also gave him narcotics. Eight weeks later when he saw his dermatologist for an unrelated problem,
and he was referred to our office. He was then treated with Gabapentin 900mg/day and three supraorbital nerve blocks over a ten-day period. At his last visit, he stated he had about 75% relief. It is important to note that the total time elapsed from the initial onset of pain to appropriate treatment was eight weeks. CASE III A 75 year old male presented to our pain clinic complaining of a constant pain in his left eye. The patient described the pain as a “red-hot poker being stuck in the eye”. Fourteen months previously he had been diagnosed with Shingles. During that period, he had been treated with the following medications: antivirals; anticonvulsants; antidepressants; non- steroidal anti-inflammatories; narcotics and topical creams. Since coming to the pain center, he has undergone six interventional procedures including cryotherapy of the left supraorbital nerve. Despite these many procedures, the patient noted no significant relief and continues to complain of significant pain as described above. Case IV A 35 year old male presented to our pain clinic with a six month history of intractable chest well pain. He had experienced a minor case of shingles 6 months earlier, initially associated with minimal pain. However, over the next few weeks, the pain became progressively worse, to the point that he could no longer keep a shirt on despite oxycodone 40 mg BID. He eventually required 300 mg of methadone and 6 grams of Keppra to be able to return to work. He has had no relief with multiple injections, and he is considering a spinal cord stimulator. Outcome data A review of records billed with the ICD-9 code 035.9 (shingles or postherpetic neuralgia) for a 6 month period revealed 15 patients. Patient Age length Location Pain degree # of inj
Patient 6 was an HMO patient who was approved for the initial treatment (which gave good relief) but was not approved for follow-up treatment when her lesions reoccurred 2 weeks later. Subsequent treatment was delayed for more than eight weeks, and she has required cryoneuroablation of the intercostal nerves. Interventions Patients presenting to our office with supraorbital lesions are offered supraorbital nerve blocks with deposteroid and local anesthetic (1/2cc total volume). Cervical paravertebral nerve blocks and occasionally cervical epidural steroids are used for upper extremity lesions. Thoracic shingles patients are offered a paravertebral nerve block, followed by a thoracic epidural if complete relief is not obtained. Lumbosacral lesions are treated with lumbar or caudal epidural steroids. In addition to the injection, patients are started on a topical ketoprofen-lidocaine compounded salve as well as samples and a prescription for oral gabapentin (Neurontin®). Most have already been started on antivirals before they reach our office, but if not, they may be given antivirals as well. It has been extremely gratifying to treat the active shingles patients, especially those in extreme pain. Within moments after the injection the pain is gone, and for most patients pain never returns or returns at a much decreased level. The erythema and swelling are markedly decreased by the second visit 2 to 3 days later, and the lesions are usually drying up within that timeframe as well. If there is not complete relief, the patient is offered a second (and rarely, a third or fourth) injection. Implications As the US population ages, the incidence of shingles (and therefore post herpetic neuralgia) would be expected to increase. The economic impact of lost wages is hard to quantify, especially in a retired population. However, the expected increased utilization of medical resources can be significant, both initially and long term. Early interventional treatment is effective and provides rapid and often complete relief. Extensive workups before the lesions appear, analgesics for the acute pain, and then expensive treatments such as spinal cord stimulation for the post herpetic neuralgia all represent avoidable costs if the herpes zoster infection is aggressively recognized and treated. Because of the time issues, it is critical that patients and physicians be educated in the importance of rapid and aggressive treatment. Too often, patients are told that “nothing can be done” and that “the rash will go away on its own”. Unfortunately, pain physicians are usually used to seeing chronic pain patients, where onset of treatment is not an issue. It is not uncommon for many pain practices to have 4 to 6 week waiting times for an appointment, clearly too long to wait with this condition. Community doctors have to be educated bythe pain practitioners themselves regarding the acute interventional treatment of shingles. The entire office staff needs to be sensitized to the time critical nature of this patient population. In our practice, we lecture frequently to the family doctors in my area, explaining to them the “code word” – “active shingles” which will get their patient into my office that day or the next morning. Our staff is trained to tell patients on the phone to immediately come into the office. We have written several small articles for the local newspaper on the topic, and have even convinced one of the most difficult local HMOs to give carte blanche approval for immediate treatment of their shingles patients. Despite
these efforts, we are still referred patients with untreated pain weeks, months, and years after the lesions have healed. Conclusion: Rapid interventional treatment of acute shingles can dramatically decrease the pain of active shingles and potentially decrease the risk of post herpetic neuralgia. Although there have never been any controlled studies of interventional therapy to treat acute shingles pain or to prevent postherpetic neuralgia, injections (especially peripheral nerve blocks) are safe and reasonable in experienced hands (25). Pain management has always been the treatment of last resort, and as a result, patients suffer needlessly, and costs escalate. Treatment options for PHN are very limited, ineffective, and cost prohibitive, so early, aggressive treatment of shingles is critical. Where can I get more general information about shingles? NIH/ NINDS
Tel: 800-352-9424 http://www.ninds.nih.gov American Chronic Pain Association (ACPA) Email: [email protected]
http://www.theacpa.org Tel: 916-632-0922
Fax: 916-632-3208 National Chronic Pain Outreach Association (NCPOA) http://chronicpain.org Email: [email protected]
VZV Research Foundation [For Research on Varicella Zoster]
http://www.vzvfoundation.org [email protected]
Tel: 212-472- 3181 Tel Toll free: 800-472-VIRUS (8478) Fax: 212-861-7033
National Foundation for the Treatment of Pain
http://www.paincare.org [email protected]
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In diesem Bericht möchte ich hauptsächlich auf den Aufenthalt im Krankenhaus eingehen, weil ich denke das dies für viele auch eine Entscheidungshilfe für die Therapieform sein kann. Der Weg von den ersten Anzeichen bis zur entgültigen Diagnose SAA (Schwere Aplastische Anämie) dauerte ca. 2 Jahre. Mitte 2000 wurden bei einer Routineuntersuchung schlechte Thrombozytenwerte und nur leicht verm