Harlequin syndrome in a patient with probable hemicrania continua and exertional headache - is there a link? a case report.

BACKGROUND: The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported. CASE PRESENTATION: This work describes the case of a 42-year-old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner's syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren's syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren's syndrome. CONCLUSIONS: This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.

Diagnostic value of niacin skin blunting response in adolescent patients with depression.

OBJECTIVE: To investigate the differences in the niacin skin flushing response of adolescent depressed patients and healthy adolescents and its diagnostic value in adolescent depression. METHODS: Thirty-eight cases of acute episodes of depression in unmedicated adolescents and 47 age- and sex-matched healthy controls were included as study subjects, and sociodemographic and clinical data were collected, all of which were stimulated with six concentration gradients (up to 60 mmol/L, followed by sequential 3-fold gradient dilution to a minimum of 0.25 mmol/L) of niacin solution on the forearm skin, and the skin flushing area was applied as an assessment index. RESULTS: The total area of redness of the skin in response to niacin was significantly lower in the adolescent depression group than in the healthy adolescent group (Z=-3.36, p = 0.001) and was able to distinguish the adolescent depression group from the healthy adolescent group (area under curve = 0.713, sensitivity 51.1%, specificity 83.2%). CONCLUSIONS: Niacin sensitivity is reduced in adolescent depressed patients, and the niacin skin flush response has potential clinical value as a diagnostic biomarker for adolescent depression.

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.

Health-Related Habits and Health Promotion Behaviors in People With Alcohol Flushing.

There is limited investigation on health-related behaviors by alcohol flushing. A nationwide cross-sectional study was conducted using data from the Korea Community Health Survey. The final analysis included 130 192 adults with available information on alcohol flushing assessed by a self-reported questionnaire. About a quarter of participants were classified into alcohol flushers. After considering demographics, comorbidities, mental health, and perceived health status, multivariable logistic regression analysis revealed that flushers smoked or drank less and received vaccination or screening more than nonflushers. In conclusion, flushers have healthier behaviors than nonflushers.

Harlequin Syndrome Related to Perioperative Intercostal Blockade: A Case Report.

Harlequin syndrome is a rare syndrome characterized by hemifacial flushing and altered facial sweating, with only a few case reports related to intercostal blockades. We present a case of Harlequin syndrome in a 65-year-old woman after intercostal blockade for video-assisted thoracoscopic lobectomy. One hour postoperatively, the patient became nauseated and presented with flushing of the right half of the face with a clear line of demarcation. Within 3 hours, the flushing disappeared. In this case report, we discuss Harlequin syndrome in relation to intercostal blockade and encourage clinicians to consider this syndrome in the differential diagnosis when encountering similar symptoms.

Identification of adolescent patients with depression via assessment of the niacin skin flushing response.

BACKGROUND: Depressive disorder (DD) affects approximately 20 % of adolescents worldwide, but it is underdiagnosed due to the lack of objective biomarkers. Niacin skin flushing response (NSFR) is an objective and noninvasive biomarker of adult depression; however, its effectiveness has not been assessed in adolescents. METHODS: This study included 198 adolescents with 50 % healthy controls (HC). Linear mixed-effects model and multiple linear regression analyses were performed to assess differences in NSFR between the DD and HC groups. Logistic regression models based on NSFR were constructed, and the area under curve (AUC) was calculated to evaluate the performance of models. Spearman correlations were calculated to assess the relationships between NSFR and disease duration and hormone levels associated with puberty. RESULTS: Adolescents with DD displayed significantly attenuated and delayed NSFR compared to HC. NSFR effectively distinguished DD patients from HC with AUC values of 0.719 (sensitivity = 0.844) and 0.721 (sensitivity = 0.829) determined in the discovery and validation sets, respectively. Within the DD group, the maximum degree of NSFR was negatively correlated with the disease duration (r = -0.28, p = 0.011), and the overall degree of NSFR was positively associated with prolactin (r = 0.29, p = 0.039) and thyroxine (r = 0.29, p = 0.027) levels. LIMITATIONS: Future investigations will be necessary to confirm our results in an independent sample set. CONCLUSIONS: This study provides the first evidence of the utility of NSFR as an objective auxiliary diagnostic biomarker for adolescent depression. It provides new clues to understand the pathophysiology of the disease, and helps promote precise diagnosis, treatment, and prognostic evaluation of adolescent depression.

Attenuated niacin skin flushing response in children and adolescents with mental disorders: A transdiagnostic early warning marker.

Mental disorders are the leading cause of disability in children and adolescents worldwide, but among the difficulties that pediatric mental health faces is a lack of objective biomarkers used for early identification or diagnosis. Studies to date indicate that niacin skin flushing response (NSFR) could be a biomarker for adult patients with schizophrenia and affective disorders. However, there are limited data on NSFR in pediatric patients with mental disorders. This study provides the first evidence of NSFR as a potential transdiagnostic marker in pediatric patients with schizophrenia (SZ), bipolar disorder (BD), depressive disorder (DD) and autism spectrum disorder (ASD). We conducted 10-min niacin skin flush tests on 227 pediatric participants, including 59 SZ patients, 23 BD patients, 57 DD patients, 40 ASD patients and 48 healthy controls (HCs). Group, time and the concentrations of aqueous methyl nicotinate had significant effects on the flush scores. Pediatric patients with BD, DD, and SZ clustered together, while ASD patients appeared to be more similar with HCs. SZ, BD and DD groups had lower flush scores than HCs, while ASD group had higher scores than BD and DD groups. These findings suggested NSFR was blunted in pediatric SZ, BD and DD and was distinct in ASD from the other disease groups. Our data demonstrate NSFR could be a transdiagnostic marker for pediatric SZ, BD and DD, which would help to identify a subgroup of patients sharing dysfunctions of membrane phospholipids. Besides, NSFR might have potential for early identification of affective disorders from ASD.

Differential diagnosis of a thyroid mass, facial malar rash and ptosis on the flora in the primavera by Sandro Botticelli (1445-1510).

PURPOSE: The Primavera is considered amongst the greatest and controversial artistic masterpieces worldwide painted by renaissance artist Sandro Botticelli. The aim was to identify any underlying medical foundations for the painting. METHODS: Observational study. RESULTS: The painting reveals, a 'butterfly' malar rash, bilateral ptosis and a clear neck swelling consistent with a goitre in the figure of Flora. This could be explained by concomitant Graves' disease and systemic lupus erythematosus, or other presentations of multiple autoimmune syndrome. CONCLUSION: These findings highlight the likely presentation of the earliest pictorial depictions of thyroid disease with systemic lupus erythematosus and emphasize the exactitude of depiction demonstrated by Botticelli in renaissance era.

A potential objective marker in first-episode schizophrenia based on abnormal niacin response.

The lack of objective diagnostic markers has long been a challenge in the clinical management of schizophrenia (SZ). The current bivariate cut-offs method is an objective quantification of niacin skin flush abnormality (NFA) for identifying the SZ subgroup. However, the sensitivity of approximately 30% limits the application of NFA as a marker for detecting SZ. A laser Doppler flowmeter was employed to test the niacin skin-flushing response in 123 patients with first-episode psychosis including first-episode SZ (FES, n = 82) and psychotic bipolar disorders (PBP, n = 41), and non-psychiatric comparisons (NPC, n = 80). We modified the bivariate cut-offs using a combination of the niacin concentration corresponding to the half-maximal blood flow response (EC50) and a new quantitative indicator called the overall trend area (OTA). The NFA used this study method predicted FES in the NPC group with 57% sensitivity, 89% specificity, and 73% accuracy compared to the 28% sensitivity, 91% specificity, and 59% accuracy of the existing method. This novel method could discern FES from the PBP group with an accuracy of 62%, compared with the 45% of the old method. In addition, we also discuss whether the bivariate cut-offs were occasional by adjusting the cut-offs threshold. The experimental results showed that the sensitivity and specificity were most stable when using the study method. The study indicates that NFA using modified bivariate cut-offs may be a potential objective marker in FES, and the niacin skin test could be feasible for early diagnosis and treatment of SZ.

Successful treatment of idiopathic Harlequin Syndrome with oxybutynin and propranolol.

Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.

Harlequin syndrome in a young girl: An opportunity to rethink the terminology.

Harlequin syndrome is a rare disorder of the autonomic nervous system, presenting as unilateral reduced flushing and sweating of the face induced by exercise, stress, or heat. It is caused by a cervical sympathetic deficit located at the preganglionic or postganglionic level on the non-flushing side. We present a case of an 8 year old with harlequin syndrome and review the other dermatological conditions for which the term "harlequin" is part of the nomenclature.