History
Herpes zoster (shingles) may begin with a systemic response (eg, fever, anorexia, and lassitude), though symptoms frequently are mild and may not be associated by either patient or physician with the classic manifestations of the condition.
Symptoms typically include prodromal sensory phenomena along 1 or more skin dermatomes lasting 1-10 days (average, 48 hours), which usually are noted as pain or, less commonly, itching or paresthesias. [3] Prodromal pain typically is described as muscle or toothachelike in origin but may simulate headache, iritis, pleurisy, brachial neuritis, cardiac pain, appendicitis or other intra-abdominal disease, or sciatica. This simulation can result in incorrect tentative diagnoses; however, the dermatomal distribution usually helps clarify the diagnosis.
The prodromal interval of pain prior to onset of cutaneous findings has been believed to represent spread of varicella-zoster virus (VZV) particles along sensory nerves; however, approximately 10% of patients report the simultaneous onset of pain and rash.
After the onset of prodromal symptoms, the following signs and symptoms occur:
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Patchy erythema, occasionally accompanied by induration, in the dermatomal area of involvement
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Regional lymphadenopathy, either at this stage or subsequently
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Grouped herpetiform vesicles developing on the erythematous base (the classic finding)
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Pain in the dermatomal area of involvement may remain the same as in prodrome or may change in character and intensity with the onset of other symptoms; many patients describe the pain as burning, throbbing, or stabbing in nature; it may be severe, mild, constant, rare, or felt as another sensation such as pruritus; the involved area may be tender to palpation [1]
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Vesicular involution – Vesicles initially are clear but eventually cloud, rupture, crust, and involute, a process that may be greatly accelerated by treatment
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After vesicular involution, slow resolution of the remaining erythematous plaques, typically without visible sequelae – Note, however, that scarring can occur if deeper epidermal and dermal layers have been compromised by excoriation, secondary infection, or other complications
Unfortunately, resolution of the associated pain does not always accompany resolution of erythema and vesiculation. Postherpetic neuralgia (PHN), which usually is confined to the area of original dermatomal involvement, can persist for weeks, months, or years and is often severe. Severe prodromal pain and the density of the herpetic eruption have been characterized as risk factors and predictors for PHN. [56]
The reason why some patients with zoster experience PHN and others do not is not fully understood, but it is clear that patients who are older (> 60 years), particularly those who are debilitated or arteriosclerotic, are affected far more frequently than younger patients are. In addition, PHN is observed more frequently after cases of herpes zoster ophthalmicus (HZO) and in instances of upper-body dermatomal involvement.
Other less common postherpetic sequelae include hyperesthesia or, more rarely, hypoesthesia or anesthesia in the area of involvement.
Herpes zoster oticus (Ramsay Hunt syndrome) may produce an acute jugular foramen syndrome. [57] It is characterized by acute-onset dysphagia and dysphonia, often accompanied or preceded by cranial, cervical, or pharyngeal pain. Herpetic vesicles on the skin or mucosa may or may not occur, may be noted late after onset, or may go undetected.
Physical Examination
Classic physical findings include painful grouped herpetiform vesicles on an erythematous base confined to the cutaneous surface innervated by a sensory nerve (see the first image below). Typically, the condition affects a single dermatome, most commonly a thoracic dermatome, on one side of the body (see the second, third, and fourth images below). Regional lymphadenopathy may be present.
Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.
After a prodromal illness, erythematous macules and papules appear (see the image below) and progress to vesicles within 1 day. The vesicles eventually cloud, rupture, crust, and involute. Patients may experience pain and sensory loss in the distribution of the rash. Motor weakness, especially in lumbar and cervical radicular distributions, is often present but unrecognized and represents viral activity beyond the sensory root. Because the weakness often is not diagnosed accurately, the incidence and prevalence are uncertain.
Maculopapular rash due to herpes zoster in child with history of leukemia. Image courtesy of Centers for Disease Control and Prevention (CDC).
Note that zoster may present in multiple dermatomes and possibly bilaterally (ie, zoster multiplex). The frequency of multiple, disseminated, and visceral zoster is increased in the immunocompromised population. Occasionally, patients experience paresthesias and pain in a dermatomal distribution without a rash (ie, zoster sine herpete).
Many clinical variations are possible. The following is a summary of the more important variations.
Herpes zoster ophthalmicus
HZO results from viral invasion of the Gasserian ganglion and accounts for 10-15% of zoster cases. [58] In addition to the classic symptoms and lesions of herpes zoster, common manifestations of HZO include conjunctivitis, scleritis, episcleritis, keratitis iridocyclitis, Argyll-Robertson pupil, glaucoma, retinitis, choroiditis, optic neuritis, optic atrophy, retrobulbar neuritis, exophthalmos, lid retraction, ptosis, and extraocular muscle palsies.
HZO develops when cranial nerve (CN) V (ie, the trigeminal nerve) is involved in viral reactivation. For unknown reasons, involvement of the ophthalmic branch of this nerve (V1) is 5 times as common as involvement of the maxillary branch (V2) or the mandibular branch (V3). HZO is easily recognized on the basis of vesicular and erythematous involvement of the CN V1 dermatome, ipsilateral forehead, and upper eyelid (see the image below). When lesions are found in the CN V1 dermatome, a slit-lamp examination is done to identify corneal findings.
Herpes zoster in ophthalmic (V1) distribution of trigeminal nerve. Note unilateral distribution of rash and how V1 distribution may extend to tip of nose. Though at risk for keratitis with zoster in this distribution, patient had normal ocular examination. Patient consented to picture distribution for educational use; written permission on file. Image courtesy of JS Huff.
Ipsilateral preauricular and, occasionally, submaxillary nodal involvement is a common prodromal event in HZO and often is valued equivalently with pain, vesiculation, and erythema in establishing a diagnosis. Prodromal lymphadenopathy should not be confused with the later reactive adenopathy caused by secondary infection of vesicles. Headaches, nausea, and vomiting also are common prodromal symptoms.
Signs of meningeal irritation may be present; therefore, meningitis must be excluded. CN V1 (with ciliary ganglion) sends branches to the tentorium (the recurrent nerve of Arnold), as well as to CN III, CN VI, and occasionally CN IV. This may account for the frequency of meningeal signs and the occasional CN III and CN VI nerve palsies associated with HZO.
Aggressive treatment and follow-up monitoring are required for HZO because of the possibility of eye involvement, which occurs in about 50% of HZO patients. Traditionally, nasociliary branch involvement, characterized by vesicles at the tip of the nose, has indicated that eye involvement is present or imminent (the Hutchinson rule). This rule is now being disputed, with some experts claiming that eye and nasociliary branch involvement can be present without such vesiculation. In our experience, eye lesions are rare in the absence of distal nose lesions.
In the absence of prompt detection and treatment, eye involvement poses a risk to vision. The presence of orbital edema is an ophthalmologic emergency, and patients must be referred immediately for specialized ophthalmic evaluation and treatment. Iritis, iridocyclitis, glaucoma, and corneal tissue ulcerations are possible in these cases. Involvement of the area below the palpebral fissure alone, without upper eyelid or nasal involvement, is considered less likely to result in ocular complications, in that the superior maxillary nerve innervates the lower eyelid.
Postherpetic complications are more common in HZO than in other manifestations of zoster. [59] In particular, PHN is observed in well over 50% of patients with HZO and can be severe and long-lasting. Scarring also is more common, probably as a result of severe destructive inflammation.
As noted (see above), palsy of CN III and, occasionally, of CN IV and CN VI may occur. Rarely, simultaneous involvement of other CNs has been reported. The most common such event is CN VII involvement, which may produce facial palsy.
Svozilkova et al reported 1 case of varicella-caused retinal necrosis after ocular trauma. [60]
Intraoral herpes zoster
HZO may involve the skin or the oral cavity, or both simultaneously. Trigeminal herpes zoster with Ramsay Hunt syndrome may produce cutaneous, intraoral, and otic vesicles; hearing loss; and mild facial palsy. [16] Herpes zoster of the maxillary division of the trigeminal nerve may begin with toothache during its prodromal stage, followed by its vesicular eruption. [61] Herpes zoster maxillaris may involve a unilateral maxillary canine to resemble pulpal necrosis and apical periodontitis. Thus, gingival herpes zoster may be evident as painful desquamative vesicles or a pulpal disorder. [62]
Herpes zoster of maxillary branch of CN V
Involvement of CN V2 is localized to the ipsilateral cheek, the lower eyelid, the side of the nose, the upper eyelid, the upper teeth, the mucous membrane of the nose, the nasopharynx, the tonsils, and the roof of the mouth. At times, only the oral mucous membrane is involved, and there are no cutaneous manifestations. Early preeruptive herpetic pain can simulate a severe toothache and result in unnecessary oral surgery or dental treatment.
Herpes zoster of mandibular branch of CN V
Areas of CN V3 involvement include the side of the head, the external ear and external auditory canal, the lower lip, and a portion of the oral mucosa. As when other branches of CN V are involved, prodromal pain in affected areas can result in incorrect diagnoses.
Herpes zoster oticus
Herpes zoster oticus (also termed geniculate zoster, zoster auris, Ramsay Hunt syndrome, or Hunt syndrome) may develop if the geniculate ganglion is involved. This condition is considered rare but more likely is just rarely recognized. It often is mistaken for eczema, Ménière disease, Bell palsy, stroke, and abscess of the ear.
Classically, herpes zoster oticus begins with otalgia and herpetiform vesicles in the external ear canal or on the tympanic membrane, with or without features of facial paralysis resulting from facial nerve (CN VII) involvement, auditory symptoms (eg, deafness), and vestibular symptoms in variable combinations. The syndrome also may result from zoster originating from CN IX or CN X; the external ear has complex innervation that includes branches of several CNs (CN V, CN VII, CN IX, and CN X), as well as vertebral nerve C2 and possibly C3.
Glossopharyngeal and vagal herpes zoster
Glossopharyngeal zoster (herpes pharyngis) and vagal zoster (herpes laryngis) involve the jugular and petrosal ganglia, which are adjacent and often involved in some combination; however, individual involvement of both ganglia has been observed. Painful vesicular rash typically involves the palate, posterior tongue, epiglottis, tonsillar pillars, and, occasionally, the external ear. A unilateral distribution can distinguish this variation of zoster from herpes simplex and herpangina.
Herpes occipitocollaris (vertebral nerves C2 and C3 involvement)
Herpes occipiticollaris involves the posterior scalp, the nuchal area, portions of the ear, and portions of the lower mandible and anterior neck (see the image below). Vertebral nerves C2 and C3 often are involved together. Branches of these 2 vertebral nerves communicate with CN VII and CN X, sometimes causing symptoms related to these cranial nerves as well.
Nuchal or scalp involvement occasionally is confused with folliculitis, furunculosis, cellulitis, erysipelas, or acne keloidalis nuchae. The painful prodrome can result in confusion and misdiagnosis until the classic vesicular rash appears.
Herpes zoster encephalomyelitis
Herpes zoster encephalomyelitis may give rise to localized mild leptomeningitis in the region of neurologic involvement. This is more common than is generally recognized and often results in pleocytosis in the cerebrospinal fluid (CSF). Leptomeningitis most likely occurs when CNs (especially CN V) are involved because of the presence of the recurrent nerve of Arnold, which branches from CN V1 to the tentorium. For this reason, meningeal symptoms (eg, headache, changes in sensorium, fever, and neck stiffness) are most common with HZO.
Rarely, symptoms of meningoencephalitis may be significant; at times, they may be severe enough to cause death. Westenend and Hoppenbrouwers reported fatal hemorrhagic encephalitis in an otherwise healthy woman. [63] Zoster encephalomyelitis may be mistaken for acute poliomyelitis. The spread of VZV to the central nervous system (CNS) also may occur during suppression of host resistance by neoplasms, by cytotoxic drugs, and, possibly, by radiation therapy.
Herpes zoster myelitis
That VZV can produce encephalomyelitis is well documented. More rarely, the myelitis lesion predominates or is the sole feature. The clinical picture is one of acute onset of paraplegia resulting from a diffuse involvement of the spinal cord. The picture is that associated with acute transverse myelopathy.
Spinal cord involvement becomes apparent within 2-3 weeks of the initial rash, with myelopathic findings (usually bilateral) on examination. The disease may progress for 3 weeks, though a few cases of progression for as long as 6 months have been reported in patients with AIDS. Recurrent zoster myelitis is rare, though one case has been reported of a previously healthy young woman who developed recurrent myelopathy at the same spinal level. The condition resolved fully with intravenous (IV) acyclovir treatment.
Disseminated herpes zoster
Disseminated herpes zoster is usually defined as a generalized eruption of more than 10-12 extradermatomal vesicles occurring 7-14 days after the onset of classic dermatomal herpes zoster. Typically, it is clinically indistinguishable from varicella (chickenpox). Dissemination occurs in approximately 2% of zoster cases in the general population but has been observed in as many as 35% of patients who are hospitalized or immunocompromised.
Dissemination often is an indication of depressed cell-mediated immunity caused by various underlying clinical situations, including malignancies, radiation therapy, cancer chemotherapy, organ transplants, and long-term use of systemic corticosteroids (short-term use of low-to-moderate doses of corticosteroids does not increase the incidence of dissemination). Patients in whom zoster has disseminated must be observed carefully for the development of pneumonitis and encephalitis, which can be life-threatening.
Unilateral herpes zoster involving multiple dermatomes
Involvement of more than 1 dermatomal distribution in unilateral zoster is rare and usually is considered a harbinger of significant compromise of the immune system caused by AIDS, malignancy, chemotherapy, and other factors. Involvement of 2 dermatomes may be referred to as zoster duplex, and involvement of 3 or more may be referred to as zoster multiplex.
Bilateral herpes zoster
On rare occasions, herpes zoster manifests bilaterally. Bilateral presentations should always raise concern for disseminated disease (and immunocompromise) or for alternate diagnosis, specifically for herpes simplex.
In cases of bilateral zoster, it is not unusual for 1 or 2 adjacent dermatomes to be involved. Unlike examples of multiple dermatomal involvement in unilateral disease (see above), involvement in adjacent dermatomes is not typically a sign of underlying disease (eg, malignancy).
Recurrent herpes zoster
Recurrences of herpes zoster do occur rarely and are not limited to those who are immunocompromised. [64] The incidence rate of herpes zoster is 5.1 cases per 1000 person years; its recurrence rate was calculated at 12 cases per 1000 person years. Risk factors include old age (51-70 years) and zoster-related pain longer than 30 days. Many reputed cases of recurrent zoster involve other entities, usually herpes simplex in a linear distribution.
Herpes zoster involving urinary bladder
Rarely, zoster involving the dermatomes of the buttock area (vertebral nerves L1, L2, S2, S3, S4) may be associated with vesicles in the bladder, which can cause severe dysuria and urinary frequency. This picture is easily mistaken for that of cystitis. If vesicles rupture in the bladder, hematuria (another common symptom of cystitis) may occur. Transient bladder paralysis resulting from zoster involving the gluteal and sacral regions and lumbar sympathetic segments has been reported, and acute urinary retention is possible if a motor component exists.
Herpes zoster involving other internal structures
Vesicular involvement has been reported in bronchi, pleural spaces, and the gastrointestinal (GI) tract. Zoster pneumonia also has been reported. Such involvement frequently is found in individuals with significantly compromised immune systems. Pain in these areas, like pain on the cutaneous surface, may be referred and does not necessarily indicate the presence of vesicles.
Herpes zoster with motor complications
Although VZV typically invades only sensory nerves (for unknown reasons), viral particles occasionally cross over to the anterior horn of the involved ganglion and cause motor symptoms. These symptoms range from weakness to total paralysis, depending on how many roots of the involved nerve plexus are affected. Whereas most motor involvement (like most sensory involvement) is self-limited, partial or complete paresis can persist indefinitely, particularly when cranial (CN V or VII), phrenic, and extremity nerves are affected.
Paresis may be seen in extraocular muscles, any area of facial innervation, and anywhere along the spinal cord, including the phrenic nerve. Paresis most commonly is observed when muscles of an arm or leg are involved; however, this may be because it is detected most easily at those locations.
Fabian et al reported a patient who had a left upper arm monoplegia after zoster multiplex involving C4, C5, and C6 nerves. [65] The authors believed that the brachial plexus inflammation was an extension of a dorsal ganglionitis. They found that the motor neuropathy was an inflammatory demyelinating process.
Truncal motor involvement may be more common than generally is believed, because both physician and patient easily may overlook a small area of muscle weakness of the central trunk. Paralysis of abdominal musculature can cause a hernial bulge.
Zoster sine herpete
Some cases of VZV reactivation result in a condition known as zoster sine herpete. Patients experience pain and weakness in a dermatomal distribution, and a tender, erythematous, unilateral patch or plaque is apparent, but there are no visible signs of cutaneous vesicles. Like typical herpes zoster (shingles), zoster sine herpete tends to be preceded by dysesthesias.
This condition presents a diagnostic dilemma; however, VZV DNA may be detected by polymerase chain reaction (PCR) assay of oropharyngeal swabs in patients with zoster peripheral facial palsy. Because such studies are not routine, the true incidence and prevalence are unknown. Furuta et al found that VZV could be demonstrated in 8-25% of patients with acute peripheral facial palsy without cutaneous vesicles. [66]
Complications of Herpes Zoster
Although it is rarely, if ever, fatal in itself, it may be considered a contributing factor to death in some individuals who are severely debilitated. Westenend and Hoppenbrouwers reported fatal hemorrhagic encephalitis in an otherwise healthy female. [63] The condition has numerous potential nonfatal complications, as follows.
PHN is the most common complication, affecting as many as 50% of patients older than 60 years. It may develop as a continuation of the pain that accompanies acute zoster, or it may develop after apparent resolution of the initial zoster reactivation. The pain may last for months to years. [5] The underlying pathophysiology of PHN may involve peripheral nerve damage or continued viral activity.
Herpes zoster involving CN V1 (ie, HZO) may be associated with conjunctivitis, keratitis, corneal ulceration, iridocyclitis, glaucoma, and decreased visual acuity or blindness. With ocular involvement, long-term antiviral treatment may be required.
Complications of herpes zoster oticus (Ramsay Hunt syndrome)—that is, zoster involving CN V, CN IX, and CN X)—may include peripheral facial nerve weakness and deafness. This condition may also produce an acute jugular foramen syndrome. [57]
It may be associated with a secondary bacterial infection at the site of the rash (typically streptococcal or staphylococcal). Necrotizing fasciitis is a possible and devastating complication.
Meningoencephalitis secondary to herpes zoster is more likely to be seen in immunocompromised patients than in immunocompetent patients. Other CNS complications may include myelitis, cranial nerve palsies, and granulomatous angiitis. Granulomatous angiitis may result in the development of a cerebrovascular accident.
Disseminated zoster may be seen in immunocompromised patients. In such cases, hematogenous spread may result in the involvement of multiple dermatomes.
Visceral involvement can also occur. Hong and Elgart have reported GI complications. [67]
Guillain-Barré syndrome is a rare complication from reactivation of latent VZV. Cresswell et al reported that Guillain-Barré syndrome also resulted from primary VZV infection in an adult. [68]
VZV is being investigated for its possible role in least some cases of chronic fatigue syndrome. [69]
Severe herpes zoster after varicella vaccination in immunocompetent young children as a rare complication has been described, with these children at low risk of developing meningoencephalitis. [70] In children, VZV infection may produce a facial palsy [71] ; it may also result in zoster sine herpete, doing so more frequently in children than adults. Ramsay Hunt syndrome (herpes zoster oticus) tends to be found more often in school-aged children, whereas zoster sine herpete is more likely to be found in preschool children.
Childhood varicella zoster virus infections have been linked with an increased risk of arterial ischemic stroke and may precipitate a childhood arterial ischemic stroke. [72, 73]
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Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.
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Suspected zoster of the hand.
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Herpes zoster, unilateral, on trunk.
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Herpes zoster on lateral part of abdomen.
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Maculopapular rash due to herpes zoster in child with history of leukemia. Image courtesy of Centers for Disease Control and Prevention (CDC).
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Herpes zoster in ophthalmic (V1) distribution of trigeminal nerve. Note unilateral distribution of rash and how V1 distribution may extend to tip of nose. Though at risk for keratitis with zoster in this distribution, patient had normal ocular examination. Patient consented to picture distribution for educational use; written permission on file. Image courtesy of JS Huff.
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Herpes zoster on neck.
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What is herpes? Herpes is a virus causing sores most commonly around the mouth (oral herpes) and genitals (genital herpes).
