Mini-Review on the Harlequin Syndrome-A Rare Dysautonomic Manifestation Requiring Attention.

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

Measuring niacin-associated skin toxicity (NASTy) stigmata along with symptoms to aid development of niacin mimetics.

Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and rubor, as well as dolor, tumor, and calor, and systemically, heat loss, frigor, chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured rubor by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and calor/frigor by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.

Developing precision medicine for people of East Asian descent.

The goal of precision medicine is to separate patient populations into groups to ultimately provide customized care tailored to patients. In terms of precision medicine, ~540 million people in the world have a genetic variant of the aldehyde dehydrogenase 2 (ALDH2) enzyme causing a flushing response and tachycardia after alcohol consumption. The genetic variant is identified as ALDH2*2 and originates from East Asian descendants of the Han Chinese. The variant is particularly important to consider when discussing lifestyle choices with patients in terms of risk for developing specific diseases, preventative screening, and selection of medications for treatment. Here we provide examples why patients with an ALDH2*2 variant need more individualized medical management which is becoming a more standard practice in the precision medicine era.

[Ovarian carcinoid tumor responsible of permanent facial erythrosis and flushings during sexual intercourse]. / Tumeur carcinoïde ovarienne responsable d'une érythrose faciale permanente et de flushs au décours des coïts.

INTRODUCTION: Ovarian neuroendocrine tumors are extremely rare. In the ovary, the term of neuroendocrine tumor is usually related to carcinoid tumors although it may be sometimes applied to neuroendocrine carcinomas of non-small cells or small cells cancers usually occurring in the lungs. These carcinoid tumors may develop de novo or from other tumors including teratomas. CASE REPORT: We report a patient who presented with an ovarian carcinoid tumor developed, near or from a dermoid cyst, which was original by its mode of discovery in the dermatology department. Indeed, the patient consulted because of permanent facial erythrosis, with flushes but also facial telangiectasias. During medical examination, classic symptoms of carcinoid syndrome including heart disease were obvious. The occurrence of flushes during coitus should evoke pelvic tumor location. CONCLUSION: A carcinoid syndrome is naturally evoked in the presence of flushes but it must also be part of the differential diagnosis in a patient with facial erythrosis or telangiectasias, especially if they are associated with diarrhea or right heart failure. The prognosis of carcinoid heart disease is considerably better in case of ovarian location than when it is a primitive carcinoid tumor of lung or from gastrointestinal tract.

Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells.

Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism. Deficiency in ALDH2 expression and function are caused by a single nucleotide substitution and resulting amino acid change, called ALDH2*2. This genetic polymorphism affects 35-45% of East Asians (about ~560 million people), and causes the well-known Asian flushing syndrome, which results in disulfiram-like reactions after ethanol consumption. Recently, the ALDH2*2 genotype has been found to be associated with marrow failure, with both an increased risk of sporadic aplastic anemia and more rapid progression of Fanconi anemia. This review discusses the unexpected interrelationship between aldehydes, ALDH2 and hematopoietic stem cell biology, and in particular its relationship to Fanconi anemia.

[Harlequin syndrome in a melanoderm patient]. / Syndrome d'Arlequin chez un patient mélanoderme.

INTRODUCTION: Harlequin's syndrome is a neurological disorder due to a dysfunction of the sympathetic innervation of the face. It has been rarely reported in the literature. The authors report one case occurring in a melanoderm patient. OBSERVATION: A 38-year-old melanoderm man, without any history of surgery or neck trauma, consulted for a strictly right unilateral facial hyperhidrosis. Clinical and radiological investigations concluded to an idiopathic Harlequin's syndrome. Therapeutic abstention was proposed because of non-invalidating symptoms. DISCUSSION: Harlequin's syndrome is a rare sudoral and vaso-motor disorder. On dark skin, flush and erythrosis may be subtle and the diagnosis less obvious. Etiologies are varied but essentially idiopathic. Its association with others dysautonomic facial syndromes is possible. Main differential diagnosis is the Frey's syndrome. Treatment is not clearly codified.

Harlequin syndrome in a patient with putative autoimmune autonomic ganglionopathy.

The author presents a patient with Harlequin and Horner syndromes as part of an autoimmune autonomic ganglionopathy and suggests implication for work-up and management. In general, Harlequin and Horner syndromes are reported to be caused by either a structural lesion of the sympathetic pathway or, when no structural lesion is found, are presumed to be idiopathic. In this paper, a 76 year old man developed a Harlequin and Horner syndromes in the setting of subacute autonomic failure and other systemic features. The patient's symptoms improved with a short course of intravenous methylprednisolone. An autoimmune etiology should be considered in patients with Harlequin syndrome and immunomodulatory treatment could be attempted, especially when there is evidence of a more generalized autoimmune autonomic ganglionopathy.

Harlequin syndrome: a mask of rare dysautonomic syndromes.

Harlequin syndrome (HS) is a rare disorder of the sympathetic nervous system which presents with unilateral decreased sweating and flushing of the face, neck, and chest in response to heat, exercise, or emotional factors. The contralateral side displays a compensatory overreaction to provide normal heat regulation of the face as a whole. In the literature, most of the cases are primary in nature and no underlying cause could be identified. Harlequin sign is used to denote these symptoms in patients who also exhibit associated oculosympathetic paresis, such as Horner syndrome, Adie syndrome, and Ross syndrome.We report a rare case of a 13-year-old boy who presented with complaints of flushing and sweating of the left side of the face after exertion, while the right side remained dry and maintained its normal color. No structural abnormality was identified on detailed work up. Thus, diagnosis of classic idiopathic HS was made. Despite the rarity of this syndrome, dermatologists should be acquainted with this distinctive entity and should refer the patient for complete ophthalmological and neurological examination.

Idiopathic harlequin syndrome: a pediatric case.

Harlequin syndrome, Harlequin sign, Holmes-Adie syndrome, and Ross syndrome lie on a spectrum of partial dysautonomias affecting facial sudomotor, vasomotor, and pupillary responses. These syndromes have imprecise clinical boundaries and overlap syndromes are known. We report a 9-year-old girl who presented with anhidrosis over the right half of her face and the left side of her body, with compensatory hyperhidrosis on the contralateral side. She was noted to have bilateral tonic pupils and normal muscle stretch reflexes with other features suggestive of autonomic dysfunction. Investigations to rule out secondary causes were noncontributory. Her clinical presentation can be categorized as partial overlap between Harlequin syndrome and Holmes-Adie syndrome.

Harlequin syndrome post-transsphenoidal pituitary macroadenoma surgery.

A 45-year-old woman, with a history of asymmetric facial flushing, was presented to the Endocrinology Unit after pituitary macroadenoma removal. After other pathological entities had been ruled out, she was diagnosed with harlequin syndrome following a lesion of the postganglionic sympathetic fibers during transsphenoidal pituitary macroadenoma surgery. We herein report the first case of harlequin syndrome following transsphenoidal pituitary surgery. We describe this difficult and benign diagnosis along with its characteristic imaging.

Coexisting harlequin and Horner syndromes after paediatric neck dissection: a case report and a review of the literature.

Harlequin syndrome, the presentation of hemifacial flushing and sweating, is a well recognized, though rarely reported, phenomenon associated with cervical sympathetic trauma. It is thought to result from disruption to sudomotor and vasomotor neurons present in the cervical sympathetic chain. The more common Horner's syndrome classically comprises the triad of unilateral miosis, ptosis and ipsilateral facial anhydrosis, and may also present as a sequela of cervical sympathetic denervation. We report a 26-month-old child with concomitant Horner's and harlequin syndromes, following neck dissection to address a large cervical lymphatic malformation. To our knowledge this is the first reported case of both syndromes resulting from surgery, and illustrates the particular challenge of lymphatic malformations in neck surgery due to their non-adherence to anatomical planes.

Upper dorsal endoscopic thoracic sympathectomy: a comparison of one- and two-port ablation techniques.

OBJECTIVE: Facial blushing and hyperhidrosis, particularly in the facial, axillary or palmar distribution, are socially, professionally, and psychologically debilitating conditions. Endoscopic thoracic sympathectomy can be carried out through multiple ports or by using a single port and a modified thoracoscope with integrated electrocautery. We reviewed our own experience to compare outcomes between these methods. METHODS: One hundred and nine consecutive endoscopic thoracic sympathectomies performed on 96 patients (M:F, 30:66) were examined with respect to operative method, symptom control, and patient satisfaction. Complete follow-up was available on 144 treated sides in 77 patients (80.2%), 38 treated with two ports, 39 performed by a one-port procedure. Mean age was 32.6 years (range 18-63) with a median follow-up of 25 months (range 5-85). Pooled data showed that the mean duration hospital stay was 1.6 nights with no deaths, conversions, or neurological injuries. RESULTS: The one-port group showed superior outcomes in terms of hospital stay, rate of postoperative pneumothorax, and the need for chest drain insertion; however, there was no correlation between number of ports and patient satisfaction. The mean overall satisfaction rating out of 5 was 3.3 with 76.6% of patients rating the outcome as 3 or more. 90.9% had an initial improvement in symptoms, although 21 patients (27.3%) described a late return of symptoms. CONCLUSION: Endoscopic thoracic sympathectomy can be safely and effectively carried out using a single port with similar results to the traditional two-port procedure. The one-port procedure may allow for a shorter duration of stay and lower complication rate.