Disseminated Herpes Zoster with a Zoster Paresis‐induced Femoral Fracture

Dear Editor, Herpes zoster usually occurs unilaterally within the distribution of a single cranial or spinal sensory nerve.1 Zoster paresis is a relatively rare complication that is characterized by focal motor weakness.2,3 Disseminated herpes zoster is defined as at least 20 lesions in multiple dermatomes and occurs mainly in patients with immunological defects such as an underlying malignancy, those undergoing immunosuppressive therapy, or those with HIV infection.4 We report this rare case of disseminated herpes zoster with zoster paresis that resulted in a femoral fracture with a review of the relevant literature. An 82-year-old woman with diabetes mellitus and hypertension developed severe burning pain in her right knee. After 3 days, a red maculopapular rash and vesicles appeared in her vulvar area and the medial side of the proximal right leg, which subsequently spread over her entire body (1, 2). At the same time, she had difficulty in walking due to weakness and pain in her right leg. The patient was diagnosed with herpes zoster by her local clinician and was treated with acyclovir 800 mg five times daily for 7 days. Despite the antiviral therapy, her symptoms did not improve. She sustained a right femur shaft fracture due to a fall while walking using the walker. Hypoesthesia and allodynia were observed in the right leg, corresponding to the L2-L4 and S1 dermatomes. Motor strength of the lower limb was such that hip flexion and knee extension were 2/5, and knee flexion, ankle dorsiflexion and great toe extension were 3/5. Degenerative changes and osteoporosis were visible on radiographs of the lumbosacral spine. An electrodiagnostic evaluation was performed. In the nerve conduction study, the sensory nerve action potentials in the right anterior femoral cutaneous nerve, the right lateral femoral cutaneous nerve, right saphenous nerve, the right superficial peroneal nerve and right sural nerve were not evoked. The right femoral motor nerve response was absent and the right peroneal motor nerve response had decreased amplitudes. Needle electromyography showed no motor unit action potentials (MUAP) in her right vastus medialis, right rectus femoris, right adductor longus and right adductor magus muscle (L2-L5 myotomes), and reduced MUAP in her right gluteus maximus, right gluteus medius, right tibialis anterior, right peroneus longus, and right gastrocnemius muscle (L4-S2 myotomes). Brownish pustules and crusted lesions on the right leg and vulva of the patient. Disseminated rashes and vesicles can be seen on the patient's trunk (a) and face (b). The serum varicella zoster virus (VZV) serology was positive for immunoglobulin (Ig) G (4.5 arbitrary unit by an enzyme-linked immunosorbent assay [ELISA], reference value: below 0.9 arbitrary unit) and Ig M (0.93 arbitrary unit by ELISA, reference value: below 0.9 arbitrary unit). The patient was diagnosed with disseminated herpes zoster with herpes zoster neuropathy and treated with intravenous acyclovir 10 mg/kg every 8 h for 5 days. The patient was then switched to oral famciclovir 250 mg three times daily for an additional 3 days. She also underwent an epidural block and the femur fracture was treated with internal fixation. The skin lesion and area of pain, hypoesthesia and allodynia decreased gradually but the muscle weakness persisted. Pharmacotherapy, epidural block, physiotherapy and rehabilitation were continued at our outpatient department. Six months after the onset of her symptoms, there was a significant improvement in pain. The right lower extremity weakness was also improved, but was incomplete. Herpes zoster, also called shingles, is a consequence of a reactivation of a latent VZV from the dorsal root ganglia.1 It is characterized by unilateral vesicular eruptions within a dermatome. The reactivation of VZV is believed to be due to waning VZV-specific T cell responses.5 Although no age group is spared, herpes zoster is more common among the elderly due to the age-related waning of VZV-specific T cell immunity.6 In patients with an active zoster infection, motor paralysis is a rare complication and is usually segmental in distribution. It has a reported frequency ranging from 0.5–5.0%.2,3 Facial paralysis after cranial herpes zoster is the most common paralysis. The second most commonly affected area is the upper limb, followed by the trunk. Lower limb involvement is rare.2,3 In the present patient, the lower limb was affected. Her herpetic eruption initially involved the vulvar area as well as the anterior and medial side of her proximal right leg, and then spread over her entire body. The neuropathy affected the L2-S2 dermatomes. The precise pathogenesis of muscular paresis that can occur after herpes zoster is unclear. However, the association between the segmental paresis and the dermatome distribution of the herpetic rash suggests viral spread from the dorsal root ganglion to the anterior horn cells or the anterior spinal nerve roots.7,8 Hanakawa et al. suggested that direct spread of the virus from the sensory ganglia to the anterior horn cells and/or the spinal nerve roots causes an inflammatory response.8 This viral-induced inflammation causes a neurological deficit as a result of hypervascularity in the perineural structures or a disruption of the blood–nerve barrier. Fabian et al. suggested that muscular paralysis is the result of the direct primary inflammatory involvement of the motor nerve.9 Disseminated cutaneous zoster is defined as more than 20 vesicles outside the area of the primary and adjacent dermatomes.4 The dissemination of herpes zoster, although extremely rare in immunocompetent patients, might be as high as 10–40% in immunocompromised hosts (HIV, cancer, patients on immunosuppressive therapy).4,5 Dissemination in immunocompetent patients appears to occur in older patients. The average age for disseminated herpes zoster in reportedly immunocompetent patients is 65.4 years.10–12 Elderly patients should be recognized as a group in whom the risk of dissemination is greater than that of an average immunocompetent host. Atypical and more severe presentations must also be expected in the oldest of the elderly. Age shows a strong correlation with the incidence of complications, such as zoster paresis and postherpetic neuralgia, and with the presence and severity of electrophysiological alterations of the motor and sensory fibers.13 In our patient, significant age-related depression in cellular immunity could have contributed to the dissemination of herpes zoster with zoster paresis. A large population-based study revealed diabetes mellitus to be a risk factor for herpes zoster.14 Moreover, Okamoto S et al.suggested that the increased risk of herpes zoster in patients with diabetes mellitus might be related to a decreased VZV-specific cellular immunity.15 However, Mondelli et al.reported that malignant neoplasms, immunosuppression, and diabetes did not correlate with the incidence and course of complications, such as zoster paresis and postherpetic neuralgia, or with the severity of electrophysiological alterations.13 Intravenous acyclovir 10 mg/kg every 8 hours for 5–7 days is the treatment of choice for disseminated zoster. Antiviral therapy of an appropriate dose and duration can reduce the incidence and severity of zoster paresis.13 Our patient had been treated with oral acyclovir for 7 days after the onset of her skin rash. However, this treatment may have been inadequate, as patients who develop motor paresis may have more extensive inflammation than that shown in normal cutaneous zoster. Despite treatment with oral acyclovir, her symptoms did not improve and she developed a right femur shaft fracture due to weakness. In conclusion, disseminated herpes zoster is a potentially serious infection that can present in the absence of immunosuppression. Moreover, the likelihood of complications and the severity of sensory and motor peripheral axonal damage increase with age. Therefore, the identification and aggressive treatment of a disseminated herpes zoster infection in elderly immunocompetent hosts is important. Early diagnosis and adequate antiviral therapy should be started as soon as possible because it appears to reduce the likelihood of zoster paresis and the severity of peripheral nervous system damage.