Definition.
Varicella-zoster virus (VZV) initial infection causes chickenpox, and after healing the residual virus lurks in the ganglia of the posterior spinal nerve roots and cranial nerves, and when VZV-specific cellular immunity decreases, the virus reanimates to occur in herpes zoster. Pain is one of the common clinical symptoms and sequelae of herpes zoster. Herpes zoster-related pain includes pain in the acute phase of herpes zoster and postherpetic neuralgia. Postherpetic neuralgia mainly refers to pain that persists for more than 4 weeks after the herpes has healed.
Mechanism.
Acute herpes zoster pain is mostly considered to be injury-receptive pain, partially accompanied by neuropathic pain. The mechanism is thought to be related to inflammatory edema and nerve fiber damage within the nerve tissue triggered by an acute episode of viral infection. Postherpetic neuralgia is a typical neuropathic pain, the exact mechanism of its occurrence is not fully elucidated, and most scholars believe that PHN is not a temporal continuation of acute herpes zoster pain. Current research can be summarized in the following three aspects: (1) peripheral mechanisms: mainly manifested by inflammation of the peripheral nerve trunk and abnormal conduction after nerve injury; (2) central mechanisms: associated with central nervous abnormalities mainly related to altered function of the thalamus on pain-regulating loops; (3) related to psychiatric factors.
Clinical features.
Abnormal skin sensation and varying degrees of pain are the most common early symptoms of herpes zoster. These symptoms can appear several days before the onset of herpes zoster, or they can occur during and after the onset of the rash. The pain is distributed unilaterally in bands, occurring in one or two adjacent skin areas, and does not cross the midline of the torso. The pain is usually burning, stabbing, or electric shock-like in nature and is often associated with nociceptive hypersensitivity. Very few patients have only pain in the dermatomes after the prodromal phase without a rash, called “rashless herpes zoster”.
Diagnosis.
An accurate diagnosis is very important. An accurate clinical diagnosis can be made based on the typical symptoms and signs of herpes zoster. A rash with asymmetrical skin areas and clustered blisters is diagnostic of herpes zoster. Other diagnostic points include: prodromal symptoms such as general malaise and malaise before the onset of the disease; burning or pins-and-needles pain or skin sensory sensitization at the affected area; distribution of the rash according to innervated areas; unilateral, but midline torso; self-limiting course of the disease, about 2-3 weeks, with pigmentary changes or scarring after healing.
Virological diagnosis in the laboratory is an important method to diagnose atypical cases and to make a differential diagnosis. VZV infections in pregnant women and newborns, atypical infections in immunodeficient patients, and suspected CNS VZV infections must be confirmed by laboratory diagnosis. Methods include.
Tzanck smear method: detects multinucleated giant cells and intranuclear inclusion bodies in skin lesion specimens, but cannot distinguish VZV from HSV infection.
Tissue culture method for direct detection of the virus: long and with false negatives, as the virus is not easily revived in the lesions.
Direct fluorescent antibody (DFA) staining of VZV-infected cells by making cell scrapings from the base of the lesion: both fast and sensitive.
VZV PCR: equipment is not widely available.
ELISA and immunofluorescence techniques for VZV-specific IgG, IgM and IgA: VZV IgG may be elevated spontaneously or in the presence of recurrent HSV infection (cross-reactivity of antigenic determinants), whereas elevated IgM and high titers of anti-VZV IgA antibodies often indicate recurrent VZV infection, with or without skin lesions.
Differential diagnosis.
Herpes zoster should be differentiated from herpes simplex and dengue. Patients with painful herpes zoster with localized pain or abnormal skin sensation without a rash (e.g., prior to rash onset or in cases of rashless herpes zoster) should be differentiated from common painful conditions in that area such as neurogenic cervical spondylosis, renal calculi, gallstones, angina pectoris, and disc herniation based on the site of pain.
Treatment.
The goal of treatment for herpes zoster-related pain is to relieve the pain and improve the patient’s quality of life.
1. Antiviral treatment
is indicated for use in the acute phase of herpes zoster. Currently applied antiviral drugs include: acyclovir, valacyclovir and famciclovir. These 3 drugs are all guanine adenosine analogues with specific affinity for the virus but low toxicity to mammalian host cells. The application of antiviral drugs in the acute phase can significantly reduce the acute skin symptoms of herpes and shorten the time frame for rash healing, while relieving the pain level.
2. Glucocorticoid therapy
In the early treatment of acute attacks of herpes zoster, the systematic application of high-dose glucocorticoids can inhibit the inflammatory process and shorten the duration of acute pain and the healing time of skin lesions, but it is basically ineffective for chronic pain (PHN). The use of corticosteroids alone is not recommended in the absence of systemic antiviral therapy.
3. Management of pain.
3.1 Acute phase pain management of herpes zoster
① Pharmacological treatment: Acute phase pain of herpes zoster has both injurious pain and neuropathic pain components. First of all, the application of acetaminophen and non-steroidal anti-inflammatory analgesic drugs can be considered. When traditional therapeutic drugs are not effective, the pharmacological treatment of postherpetic neuralgia can be referred to.
②Block therapy: local anesthetics for intradermal injection or peripheral nerve trunk or plexus block, blocking nociceptive conduction to the center, can relieve most of the acute pain of herpes zoster, and this method should be used as early as possible to achieve relief of acute pain, prevent the occurrence of PHN and relieve its abnormal pain. Commonly used nerve blocks include: (1) stellate ganglion block: for herpes zoster in the head, neck, face and upper extremities; (2) epidural block: for herpes zoster in the chest, lumbar region and sacrococcygeal region, the specific puncture site and the extent of the block should be determined by the damaged segment of the spinal nerve and the site of pain; (3) paravertebral nerve block: the corresponding nerve root is blocked separately in the damaged dermatomes; (4) other Nerve trunk and branch block
③Physical therapy.
Semiconductor laser and helium-neon laser irradiation can be used as adjunctive treatments for herpes zoster. Physiotherapy can improve blood and lymphatic system circulation and promote inflammation absorption; activate macrophages, enhance their phagocytosis and improve immune function; reduce nerve inflammation and relieve pain.
3.2 Management of postherpetic neuralgia
①Pharmacological treatment: the drugs currently used in the treatment of PHN in the band are mainly antidepressants, anticonvulsants, opioids, local anesthetics, etc. Use evidence-based medical evidence to select safe and effective drugs.
First-line drugs: tricyclic antidepressants (e.g., amitriptyline, chlorpromazine, desipramine, promethazine), 5-hydroxytryptamine and noradrenaline reuptake inhibitors (e.g., venlafaxine, duloxetine); antiepileptic drugs gabapentin and pregabalin; lidocaine patches or creams have more evidence of reducing postherpetic neuralgia and can be applied as first-line drugs.
Second-line drugs: opioid analgesics: opioid analgesics such as oxycodone, tramadol, methadone, fentanyl, capsaicin ointment, etc. may be effective for neuropathic pain. They can be applied as second-line drugs for treatment.
Third-line drugs: In addition NMDA receptor antagonists (e.g. ketamine and methadone), colistin, and cannabinoids may be used for the treatment of neuropathic pain, but more evidence-based medical evidence is needed to support them. They may be considered for application as third-line drugs.
The drug treatment of postherpetic neuralgia should fully consider safety, compliance and economy. The efficacy of drugs for postherpetic neuralgia varies from patient to patient, and the combination of drugs can be considered if necessary, and there is less evidence-based medical evidence about the combination of drugs.
Minimally invasive neurointerventional and surgical treatment
For some postherpetic neuralgia that cannot be controlled by drugs, or the control effect is not good and the patient cannot tolerate the side effects of drugs, the following techniques can be considered as appropriate.
Block therapy: trigeminal neuralgia after herpes can be considered for sexual trigeminal nerve block therapy; spinal nerve block can be considered for postherpetic neuralgia in the distribution area of spinal nerve, this is also considered for continuous epidural infusion of local anesthetics, colistin or opioids; spinal nerve root (stem, plexus) intervention is suitable for the treatment of regional pain. Interventional treatment can be performed on the corresponding nerves, such as cervical, thoracic, lumbar and sacral nerve roots, brachial plexus nerves and lumbar plexus nerves. Nerve destruction treatment is generally not appropriate; sympathetic nerve intervention: for persistent burning-like postherpetic neuralgia. Commonly used methods include: stellate ganglion block, intravenous local sympathetic block, etc. For thoracic and lumbar sympathetic ganglia and visceral plexus, physical or chemical destruction or surgical severance can be performed to achieve long-term therapeutic effect.
Neuromodulation techniques: spinal cord electrical stimulation can be tried for refractory postherpetic neuralgia; central target-controlled infusion therapy can be considered for more complicated conditions and when other treatments are ineffective, intrathecal administration (morphine, bupivacaine, colistin, baclofen, or ziconotide) via implanted pumps. Deep brain stimulation and motor cortex stimulation may be considered for certain intractable pain.
③Other treatments
In addition physical therapy such as ultrasound; psychotherapy; acupuncture and other treatments can be used as adjunctive treatment for postherpetic neuralgia in herpes zoster.