Article, Cardiology

An old lady with anterior chest pain and unilateral facial flushing

transfer to the left arm or back region. The patient did not experience any symptoms of coughing, hemoptysis, thick sputum, dyspnea, sweating, or syncope recently. In terms of physical examination, no palpable lymph node was detected near the head-neck region. As for lung examina- tion, breathing sound was normal, which was accompanied by regular heartbeat without murmur. The abdominal physical examination showed no tenderness, normal bowel sound, and no Pitting edema in the lower extremities.

Reviewing patient’s disease history, she had major depression disorder and hypertension. She also received cardiac catheterization twice due to coronary artery disease about 10 years ago in another hospital. The patient did not bring medical record with her.

Electrocardiography was performed immediately and showed normal sinus rhythm without any ST-T changes. Chest x-ray was interpreted as no distinct abnormalities (Fig. 1).

The patient was given sublingual nitroglycerin and per-oral aspirin immediately. The pain was improved after the administration of Intravenous morphine. blood test results are as follow: white blood cell, 7020 mL; hemoglobin, 11.3 g/dL; creatine kinase (CK), 26 U/L; CK-MB, 4U/L; and troponin I, 0.02 ng/mL. The EP decided to keep the patient in an observation unit with monitoring bed under the tentative diagnosis of acute coronary syndrome.

Four hours later, the cardiac enzyme follow-up results were as follows: CK, 25 U/L; CK-MB, 4 U/L; and troponin I,

0.02 ng/mL. Electrocardiography showed no evidence of change. The patient claimed that the symptom was relieved. At 12 hours into the observation, another blood cardiac enzyme test and electrocardiography follow-up examination were arranged when the patient’s chest pain aggravated again. The visual analogue pain intensity scale was 7. The vital signs were as follows: pulse rate, 84 beats/min; respiratory rate, 16 breaths/min; and blood pressure, 136/84 mm Hg. The cardiac enzyme follow-up results were as follows: CK, 36 U/L; CK-MB, 16 U/L; and troponin I, 0.01 ng/mL. Electrocardiography still suggested normal sinus

rhythm and no evidence of ST-T changes.

The EP in the observation unit suspected that the chest pain was caused by other etiology and therefore reevaluated the patient from History taking. The patient’s husband

0735-6757/$ – see front matter (C) 2012

Fig. 1 Posterolateral view of chest x-ray.

claimed that, in addition to chest pain and shoulder pain, she had also been experiencing intermittent flushing over her left face and right-eye ptosis starting since 3 days ago. Each episode of facial flushing usually lasted for about 1 to 2 hours, and no aggravating or relieving factors imposed during the episode. Besides, numbness between the second and fourth finger of the right hand was also reported.

By then, the patient had started to experience flushing and right-eye ptosis (Fig. 2). The patient did not present any other symptoms of posterior circulation insufficiency, such as vertigo, ataxia, nystagmus, hoarseness, or dys- phagia. Both pupils were of the same size and with normal light perception. There was no noticeable condition of anhidrosis, sweating, or hemianopia.

The neurologic examination revealed normal motor and sensory function over all limbs, and examination of Cranial nerves did not show any abnormalities. No localized tenderness over shoulder or arm was noted , and the pulse over wrist was also normal.

The EP contemplated the possibility of Harlequin syndrome in combination with Honer syndrome. After reviewing the chest film, increased opacity at right apical lung was impressed. Head-neck and chest CT was arranged under the suspicion of Pancoast lesion. The CT report revealed a needle-shaped heterogeneous lump in the right lung apex with a size of approximately 4.7 x 3.5 x 4.3 cm (Figs. 3 and 4). A malignant tumor was suspected. A lymphadenopathy was also observed over the right helium

Fig. 2 Picture of the patient showing flushing with right-eye ptosis.

and trachea. After the EP explained the condition to the patient, she was admitted to chest medicine ward for further assessment.

Fig. 3 Nonenhanced chest CT showing lesion over right lung apex with enlarged lymph node.

Fig. 4 Lung window of chest CT showing distinct needle-shape lump over right lung apex.

The patient underwent a systemic bone scan after admission, which indicated a possible metastasis in the first rib bone, sacrum, and left sacroiliac joint. The patient also received an ultrasound-guided fine-Needle aspiration, and the report failed to identify any malignancy. A CT- guided biopsy also failed due to patient’s poor cooperation. A mediastinoscopy was suggested, but the patient refused any more invasive procedure. She was discharged and never returned to our outpatient clinic for follow-up.

Harlequin syndrome is primarily characterized by unilat- eral facial flushing. The flushing side is usually accompanied by sweating and can be induced by heat or exercise. The condition is usually idiopathic, whereas some cases are believed to be relating to the central or peripheral sympathetic lesion located on the opposite side of flushing. The first discussion of Harlequin syndrome was brought up by Lance et al [1] as early as 1988. They described 5 cases of unilateral facial flushing accompanied by sweating, and among which 4 could be induced by exercise. It was believed that the cause of the symptom was associated with the torsional occlusion of the anterior radicular artery at the third thoracic segment. In 1993, Drummond and Lance [4] suggested that Harlequin syndrome might refer to lesions of preganglionic or postganglionic cervical sympathetic fibers and parasympathetic neurons of the ciliary ganglion. Other studies have concluded that Harlequin syndrome might be related to the effect of lung apex lesion on autonomic nerve system or central venous catheterization in the internal jugular vein [1-3]. Hemifacial anhidrosis and flushing have also been reported in patients with sympathetic nerve injuries in the eyes [4,5]. So far, other than patients

with idiopathic Harlequin syndrome, all unilateral sweating and flushing on the opposite side caused by lesions that did not affect the normal sympathetic function were considered a compensation effect of sympathetic denervation of the anhidrosis side.

Honer syndrome is characterized by symptoms of ptosis, miosis, and anhidrosis on the lesion side. Flushing is sometimes observed on the lesion side as well. Lesions that cause Horner syndrome could be found in any of the 3 sympathetic pathways [6]:

  1. First synapse: starts in hypothalamus, through brain- stem, and ends in cervical cord
  2. Second synapse: starts in cervical sympathetic trunk, through brachial plexus and lung apex, and ends in superior cervical ganglion
  3. Third synapse: ascends with the Internal carotid artery, through the cavernous sinus and oculosympa- thetic pathway, and merges with the ophthalmic division V1 of the trigeminal nerve that controls the iris dilator muscle and Muller muscle to perform actions of elevation of upper eyelid and retraction of lower eyelid.

Neurologic examination allowed us to preliminarily locate the lesion that caused Horner syndrome. We discussed the patient’s symptoms including flushing over left face, right ptosis, chest pain, and fingers numbness.

The primary cause of facial flushing was epithelial vasodilatation caused by stimuli resulting in increased blood flow. These stimuli were commonly divided as autonomic and vasodilator stimuli. Autonomic-mediated flushing was attributable to thermoregulatory factors, emotional impacts, neurological disorder, and others. Vasodilator-mediated flushing was related with rosacea, carcinoid syndrome, and Endocrine disorders. Facial flushing caused by Horner syndrome was associated with autonomic- mediated flushing.

In terms of the ptosis symptoms, other causes that may induce ptosis included neurogenic factors such as congen- ital ptosis, aponeurotic ptosis, mechanical ptosis, third nerve palsy, neuromuscular junction disorders, and myo- genic cause.

After reviewing patient’s medical history and symptoms, it was noticed that unilateral flushing and ptosis on the opposite side were unaffected by circadian time. Combining the above symptoms with chest pain, neuromuscular junction disorders and brain tumor were ruled out first. Because there were no signs of brain stem symptoms such as diplopia, vertigo, exercise disorder, and myelopathy symptoms of bilateral or unilateral asthenia, gastrointestinal and bowel movement abnormalities were observed and lesions of the brain stem or cervical-thoracic spine were unlikely. Because no abnormality over cervical vessels after performing head and neck CT and no neck pain were found, internal carotid artery dissection was excluded.

Given that the patient described a chest pain accompanied by intermittent pain in the right shoulder and numbness between the second and fourth finger of the right hand, it was highly suspected that the lesion was located at the right lung apex causing a brachial plexus compression over C5 to C8. Such speculation was further supported by the condition of Harlequin syndrome on the left face accompanied by the Horner syndrome on the right face. The flushing over her left face could be a compensation effect of sympathetic denervation over the right side.

In their report of Harlequin syndrome accompanied by Horner syndrome, Tascilar et al [7] concluded that the causes included superior mediastinal neurogenic tumor, lung apex tumor, brain stem infarction, and mastectomy with immedi- ate latissimus dorsi breast reconstruction. Nevertheless, most report still advocated an idiopathic etiology.

No noticeable anisocoria was observed in this patient, which could be due to the fact that anisocoria was more apparent in a darker environment than a brighter one. A test performed in a darker setting with the use of codeine eye drops would generate a more definitive diagnosis. A hydroxyamphetamine eye drop could be used to determine whether the lesion was a third neuron lesion but not the first or second neuron lesions.

In addition, the unilateral sweating or anhidrosis condi- tion was not significantly obvious in this patient and may become more visible under heat or exercise stimulus.

The clinical symptom of lung apex tumor varied with the extent and region of tumor compression. The most common symptoms included constant pain localized in the shoulders and scapulas proximal to the spinal cord. The pain may also extend to the arms and elbows, controlled by the ulnar nerve, or even fingers. Under a severe compression con- dition, the patient may also develop muscle atrophy. If the tumor invades the sympathetic chain and stellate ganglion, it may lead to Horner syndrome on the same side as the lesion. If the tumor compressed the spinal cord, it could also cause myelopathy. Some patients with lung apex tumor may also develop Paraneoplastic syndromes such as hypercalcemia, inappropriate secretion of antidiuretic hor- mone, and Cushing syndrome. Lung apex tumor can also present as Harlequin syndrome due to compression effect (T2, T3) [7].

The detection of lung apex tumor at the ED was possible mainly because the EP made a reevaluation after the patient’s symptoms failed to respond to the preceding treatment and repeated the history taking and physical examination thoroughly. The doctor conjectured based on the patient’s subtle facial symptoms as well as other relevant chief complaints, and arranged for necessary examination, which immediately obtained the location of the lesion.

Blind compliance in observation unit with preceding diagnosis was an important cause of delayed treatment or incidence of medical legal tragedy for the patient in ED. When the patient’s symptoms failed to improve as

anticipated after treatment, it was extremely important to reevaluate the patient. Regardless of how concrete and confirmed the Initial diagnosis was, EP should always repeat the history taking and physical examination thoroughly and also deplete all resources available to verify the information, especially the vague and unclear information, including patient’s family, caregivers at the nursing home, or even stranger witnesses. Observing and paying attention to any subtle changes in patient’s symptoms or signs were particularly important for EP to promptly identify lesions.

Shao Hwa Lin MD

Department of Internal Medicine

Wan fang Hospital Taipei Medical University Taipei 116, Taiwan, ROC

Chin I. Chen MD Department of Neurology Wan fang Hospital

Taipei Medical University Taipei 116, Taiwan, ROC

Ching Chih Liu MD Ming Hai Du MD Carlos Lam MD Emergency Department Wan fang Hospital

Taipei Medical University Taipei 116, Taiwan, ROC

E-mail address: [email protected] doi:10.1016/j.ajem.2010.09.020

References

  1. Lance JW, Drummond PD, Gandevia SC, et al. Harlequin syndrome: the sudden onset of unilateral flushing and sweating. J Neurol Neurosurg Psychiatr 1988;51(5):635-42.
  2. ten Holter JB, Visser A. Harlequin syndrome. Ned Tijdschr Geneeskd 1997;141(51):2495-9.
  3. Coleman PJ, Goddard JM. Harlequin syndrome following internal jugular vein catheterization in an adult under general anesthetic. Anesthesiology 2002;97:1041.
  4. Drummond P, Lance JW. Site of autonomic deficit in harlequin syndrome: local autonomic failure affecting the arm and the face. Ann Neurol 1993;34:814-9.
  5. Morrison DA, Bibby K, Woodruff G. The “harlequin” sign and congenital Horner’s syndrome. J Neurol Neurosurg Psychiatry 1997;62: 626-8.
  6. Kedar S, Biousse V, Newman NJ. Horner’s syndrome: last literature review version 17.2: 2009. UpToDate Online http://www.uptodate.com/ online/content/topic.do?topicKey=neuro_op/7582. Accessed August 29, 2010.
  7. Tascilar N, Tekin NS, Erdem Z, Alpay A, Emre U. Unnoticed dysautonomic syndrome of the face: Harlequin syndrome. Auton Neurosci 2007;137(1-2):1-9.

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