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CASE REPORT
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A Case of Diaphragmatic Paralysis Complicated by Herpes-zoster Virus Infection Miki Oike 1, Toshio Naito 1, Mizuha Tsukada 2, Yasumi Kikuchi 1, Naoharu Sakamoto 1, Yukiko Otsuki 1, Hiroko Ohshima 1, Hirohide Yokokawa 1, Hiroshi Isonuma 1 and Takashi Dambara 1
Abstract Diaphragmatic paralysis is commonly caused by surgical and traumatic injuries, malignant neoplasm, and neurodegenerative disorders. However, in rare instances, diaphragmatic paralysis due to herpes-zoster virus infection has been reported. Here, we describe an 85-year-old woman who developed left hemidiaphragmatic paralysis within 19 days of the appearance of a typical herpes-zoster rash involving the C4-5 dermatome on the left side. Clinical and radiological findings revealed no local causes of phrenic nerve lesion. The hemidiaphragmatic paralysis was thought to be caused by herpes-zoster virus infection. Key words: dyspnea, herpes-zoster, diaphragmatic paralysis, phrenic nerve (Intern Med 51: 1259-1263, 2012) (DOI: 10.2169/internalmedicine.51.6935)
Introduction Diaphragmatic paralysis may lead to respiratory dysfunction, and is commonly caused by surgical and traumatic injuries, malignant neoplasm, and neurodegenerative disorders (1). The association of the paralysis caused by phrenic nerve involvement with several viral infections is rare but well recognized (2). On the other hand, herpes-zoster virus infection is a common and well-known disease that causes blisters and sensory nerve neuralgia (3-6). The phrenic nerve is a branch of the cervical plexus, and is composed of fibres from C3-5. Cervical motor involvement in herpes-zoster virus infection may cause phrenic nerve dysfunction or diaphragmatic paralysis (7). Only about 30 cases of hemidiaphragmatic paralysis associated with herpes-zoster infection have been reported previously (8-29). Because hemidiaphragmatic paralysis is frequently asymptomatic and unrecognized, it is likely that hemidiaphragmatic paralysis is more common than generally appreciated. It is important to recognize the features of herpes-zoster-associated hemidiaphragmatic paralysis, which
may lead to pulmonary-function insufficiency in general practice. Therefore, further investigation and evaluation of new cases are necessary. We report a case of an 85-year-old woman with left hemidiaphragmatic paralysis complicated by herpes-zoster affecting the C4-5 dermatome, and present a review of the previous reports.
Case Report The patient, an 85-year-old woman, was referred to the department of dermatology in our hospital with burning pain and rash in her left neck, chest, and arm. She was diagnosed with herpes-zoster virus infection affecting the left C4-5 dermatome. Famciclovir was prescribed for 7 days at a dose of 750 mg per day. Nineteen days later, she complained of shortness of breath on exertion, and was referred to the department of general medicine. A chest X-ray revealed an elevated left diaphragm, and the patient was admitted to our hospital for further evaluation. She had suffered from hypertension at age 80, acute pancreatitis and cholecystitis at age 82, hyperuricemia and a renal stone at age 83 and she had undergone right side mastectomy with no adjuvant therapy
１
Department of General Medicine, Juntendo University School of Medicine, Japan and ２Department of pedeatrics, Juntendo University School of Medicine, Japan Received for publication November 14, 2011; Accepted for publication January 30, 2012 Correspondence to Dr. Miki Oike,
[email protected]
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mography showed left hemidiaphragmatic elevation, atelectasis of the left lower lobe, and small amount of pleural effusion on the left side. There was no mediastinal lymph node swelling or nodule in the mediastinum and lung field. Sputum cytology revealed no abnormalities. Bronchoscopy was not performed because of the patient’s refusal. Although no local causes of phrenic nerve lesion could be found, the patient was discharged and followed up at the outpatient clinic. After 14 months of follow-up, dyspnea and radiological findings, including chest X-ray and computed tomography, showed no alleviation. Based on clinical and radiological findings, the hemidiaphragmatic elevation was thought to be due to herpes-zoster virus affecting the C4-5 cutaneous distribution and phrenic nerve. Figure 1. Full inspiratory state
Discussion
Figure 2. Full expiratory state
for breast cancer at age 84. On admission, the following physical parameters were determined: height 142.2 cm, body weight 46.3 kg, body temperature 35.6℃, blood pressure 122/64 mmHg, heart rate 90/min, and SpO2 95% (room air). On physical examination, breath sounds were weak over the base of the left lung. The left cervical skin showed segmental distribution of pigmented herpetic scars. A well-healed surgical scar was visible on the right chest. Neurologic examination was normal. Blood gas analysis revealed the following values: pH 7.387, pCO2 39.7 mmHg, pO2 77.2 mmHg, base excess -1.0, and HCO3 23.4 mmol/L. Initial laboratory exam were unremarkable except for blood gas and renal function (blood urea nitrogen 18 mg/dL, creatinine 1 mg/dL, estimated glomerular filtration rate 40.1 mL/min/1.73 m2 as calculated by the Japanese equation for estimating glomerular filtration rate, estimated creatinine clearance 34.0 mL/min) (30, 31). Comparison of chest X-rays taken at full inspiration and expiration revealed no change in the position of the left hemidiaphragm (Fig. 1, 2). Contrast-enhanced computed to-
The present report describes a case of left diaphragmatic paralysis associated with herpes-zoster of the C4 area. Several characteristics were observed: 1) past history of right breast cancer, 2) rash and post-herpetic neuralgia, which are typically seen in herpes-zoster infection, 3) dyspnea on exertion 19 days after the onset of herpes-zoster, and 4) left hemidiaphragmatic elevation, which was not seen in the chest X-ray two months prior. Hemidiaphragmatic paralysis is often discovered incidentally by a chest X-ray obtained for some other reason. Phrenic nerve injury due to stretching or cooling during cardiac surgery is a common etiology. Cervical spondylosis, poliomyelitis, compressive tumours, pneumonia, cardiac hypothermia, diabetes mellitus neuropathy, iatrogenic embolisation, infectious neuropathies, immune-mediated neuropathies, and vasculitides are infrequent causes of hemidiaphragmatic paralysis (32, 33). A case of hemidiaphragmatic paralysis caused by herpeszoster was first reported by Halpern in 1949. We searched PubMed and Japan Medical Abstracts Society databases from 1940 to 2011 using the key words ‘diaphragmatic paralysis’, ‘phrenic nerve paralysis’, and ‘herpes zoster’. More than 30 cases have been reported to date (8-29). We limited our review to 29 English or Japanese-written cases; these cases, including the present case, revealed the following common features: 1) older age [patients in 22 of 26 cases (84.6%) were older than 55 years], 2) no sex differences [12 of 27 cases (44.4%) were male], 3) skin lesions and hemidiaphragmatic paralysis seen ipsilaterally [26 of 26 cases (100%) were ipsilateral], 4) no laterality [14 of 28 cases (50.0%) were affected on the right side], 5) associated respiratory symptoms [7 of 26 cases (26.9%) were respiratory symptom-free], 6) associated muscle weakness [9 of 24 cases (37.5%) were associated with muscle weakness], 7) past history of respiratory disease [7 of 27 cases (22.2%) had past histories of respiratory disease including bronchitis, bronchial asthma, pulmonary emphysema and lung cancer], and 8) no alleviation in many cases [6 of 22 cases (27.2%)
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Table 1. Previous Reports Author Halpern, 19498 Cervia T, 19539 Parker, 196210 Spiers, 196311 Beard, 196312 Donald, 196413 Brostoff, 196614 Pratt, 196715 Anderson, 196916 Anderson, 196916 Anderson, 196916 Anderson, 196916 Dutt, 197017 Shivalingap pa, 197018 Takagi, 1976 DerveauxL, 198219 Ueda, 1984 Hayashi S, 198420 Stowasser 199021 Melcher WL, 199022 Hayashi, 1991 Soler JJ, 199623 Fujimoto S, 199624 Paudyal BP, 200625 Manabe Y, 200726 Morinaga R, 200727 Hoque R, 200828
Age, sex 53, M M
Past history —
Site rt C3-4
Respiratory symptom dyspnea
rt upper limb, axilla lt C3-5
dyspnea
rt C3-5
none
rt cervix
none
lt C3-4
dyspnea
rt C5-6
dyspnea
65, F
hypertension, angina pectoris rheumatoid arthritis, rt lung cancer bronchitis
lt C3-5
dyspnea
56, M
bronchitis
lt cervix
none
62, F
bronchial asthma
lt cervix
dyspnea
rt cervix
cough, dyspnea dyspnea
60, F 77, F 56, M 72, F 54, M
67, F 57, F
— cholelithiasis, renal abcess rheumatoid arthritis, diabetes gastric ulcer
— —
rt cervix
none
80, F
rt C3-6 rt C4
none
lt C2-5
dyspnea
83, M
hypertension, hysterectomy CKDĺrenal transplantation chronic bronchitis pulmonary emphysema diabetes
cough, dyspnea dyspnea
59, M
diabetes, liver cirrhosis
lt cervix
none
lt cervix
cough, dyspnea dyspnea, orthopnea,
74, M 79, M
71, F
— hypertension, rt carotid endarterectomy, aortobifemoral bypass operation —
—
—
82, F
hypertension, uterine myoma
—
—
56, F
hypertension, cerebral infarction lung cancer
61,F 54, M
Bahadir C, 200829
73, F
Present case
85, F
—
— pancreatitis, cholecystitis, breast cancer
rt cervix
rt cervix
lt C2-C4 lt rt C4-5 neck
rt C4 rt cervix lt chest, neck blt shoulders lt C3-5
lt C4-5
—
lt deltoid muscle weakness
1y
— lt upper limb muscle weakness — —
lt C4-5
— — — —
—
Observation period 2y
—
rt upper limb muscle weakness
angina pectoris
74, M
—
—
74, F
32, M
Associated symptom
4w — 5y 4m 1y 8y 6m 4y 4y 1y 6m 2y
lt upper limb muscle weakness
1y
—
—
lt deltoid muscle weakness Brown-Sequard syndrome lt upper limb muscle weakness
1y
—
— 1y 4m
Antiviral therapy — — — — — — — — — — — — — — — — — — —
Diaphragmatic paralysis not alleviated — alleviated alleviated — not alleviated not alleviated not alleviated alleviated not alleviated not alleviated not alleviated not alleviated not alleviated — alleviated alleviated not alleviated not alleviated
lower extremity edema, daytime hypersomnolence
12m
dyspnea on exertion
lt deltoid muscle weakness
1y
administered
not alleviated
—
—
—
—
—
dyspnea on exertion
—
—
—
dyspnea on exertion none orthopnea
— blt deltoid and biceps brachii muscle weakness lt shoulder and proximal arm muscle weakness
dyspnea
dyspnea on exertion
were alleviated]. Details are shown in Table 1. Several studies have shown that the age is the most important risk factor for the development of herpes-zoster and
—
—
Unclear
—
—
not alleviated
not alleviated
—
—
—
1y
administered
alleviated
Until death
administered
not alleviated
19m
administered
not alleviated
1y
9m
— administered
not alleviated
not alleviated
postherpetic neuralgia (34-36). Although there is no significant difference in the age compared to postherpetic neuralgia, many patients with hemidiaphragmatic paralysis compli-
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cated by herpes-zoster tend to be of older age. Crausman et al. reported three cases of subacute unilateral diaphragmatic paralysis with a history of subacute or acute onset of neck or shoulder pain (37). All three cases were empirically treated with antiviral therapy, which resulted in alleviation. Reviewing the previous cases, antiviral therapy was administered in five cases including present case, and only one of the five cases reported alleviation. However, as for the present case, the patient had been given famciclovir for 7 days at a dose of 750 mg per day, which is not the maximum dose for this patient (recommended amount of famciclovir is 500 to 1,000 mg per day for patients with an estimated glomerular filtration rate 10 to 50 mL/min) (38). This amount of famciclovir might have been related to the association of diaphragmatic paralysis. Further development of the treatment of this disease is required. Zoster vaccine reduces the risk for developing zoster and it is efficacious for preventing post herpetic neuralgia (39). Although there is no evidence indicating that vaccination protects the sequelae including neurological disorder (40), evaluation of the efficacy of the zoster vaccine to prevent diaphragmatic paralysis is also needed. We encountered a case of hemidiaphragmatic paralysis complicated by herpes-zoster virus infection. When examining patients with herpes-zoster, particularly patients of older age and those with a past history of respiratory disease, a primary care physician needs to be aware of herpes-zosterassociated hemidiaphragmatic paralysis, which may lead to dyspnea on exertion and muscle weakness. Although antiviral therapy may be helpful, further development of the treatment of this disease is necessary. The authors state that they have no Conflict of Interest (COI).
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