Sharathkumar and Castillo-Caro Pediatric Rheumatology 2011, 9:16 http://www.ped-rheum.com/content/9/1/16 CASEREPORT Open Access Primary Raynaud’s phenomenon in an infant: a case report and review of literature Anjali A Sharathkumar1* and Paul Castillo-Caro2 Abstract Raynaud’s phenomenon (RP) is an extremely unusual finding in early infancy. In the present report we describe a one-month-old previously healthy male infant who presented with unilateral acrocyanosis. Although infantile acrocyanosis is known to be a benign and self-resolving condition, it is generally bilateral and symmetric. The unilateral nature of the acrocyanosis was an atypical finding in this infant. Consequently, he was closely monitored to evaluate the progression of his acrocyanosis. Based on his benign clinical course and failure to demonstrate other etiologies contributing to his acrocyanosis, he was diagnosed to have primary RP. Due to the rarity of RP in children, we review the progress in understanding the pathophysiology, epidemiology and management of RP and additionally discuss the differential diagnosis of unilateral and bilateral acrocyanosis in infants. Background serious conditions, the differential diagnosis of unilateral Raynaud’s phenomenon (RP) was first described by and bilateral acrocyanosis in infants is also discussed. Maurice Raynaud in 1862 [1]. Classically, the initial description of RP involved triphasic color changes in the Case report digits, with blanching (white) leading to cyanosis (blue) A one-month-old healthy male infant was brought to his followed by reactive hyperemia (red) [2,3]. However, it pediatrician’s office for the evaluation of bluish to black- has been realized that not every patient experiences all 3 ish discoloration of his left hand. His mother inciden- phases of color change and the majority of patients pre- tally noted this color change while she was changing his sent with uniphasic color change involving an isolated diaper. She did not recall any trauma or insect bite. She bluish discoloration of digits commonly known as acro- denied using naphthalene balls in the storage area for cyanosis [4-6]. Unlike RP, acrocyanosis is a common the infant’s clothes. This history was helpful to exclude phenomenon in infants and young children [4-7]. Acro- methemoglobinemia as exposure to naphthalene balls cyanosis is generally bilateral, symmetric and involves can cause infantile acrocyanosis [7]). He was breast-fed hands and feet. Since infantileacrocyanosisisabenign and his mother was the primary care taker. The infant’s and self-resolving condition, it does not require medical birth history was unremarkable except for neonatal phy- attention [7,8]. Rarely, acrocyanosis in infants can be siological jaundice treated with phototherapy for 5 days. caused by RP and may require immediate medical atten- His past history was noteworthy only for a history of tion to prevent complications of RP [9-13]. In this constipation. His family history was significant for report, we describe an infant who initially presented ischemic heart disease at a young age (< 55 years old) in with unilateral acrocyanosis and was diagnosed to have multiple members of his father’s family. His father died primary RP based on his subsequent clinical course. In at the age of 42 years due to a massive myocardial view of the rarity of RP in infants and young children, infarction. His mother had a history of migraines. He the literature about RP is reviewed with a specific focus had three healthy siblings (three brothers, ages 11, 10 on the pediatric population. To help differentiate benign and 8 years). acrocyanosis from acrocyanosis associated with other Upon arrival at the outside hospital, he was an alert and healthy infant in no acute distress. His physical * Correspondence: [email protected] examination was normal including vital signs, growth 1Department of Pediatrics, Children’s Memorial Hospital, Northwestern and development except for acrocyanosis of his left University’s Feinberg School of Medicine, Chicago, IL, USA Full list of author information is available at the end of the article hand with a clear demarcation at the wrist. His left © 2011 Sharathkumar and Castillo-Caro; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sharathkumar and Castillo-Caro Pediatric Rheumatology 2011, 9:16 Page 2 of 6 http://www.ped-rheum.com/content/9/1/16 palm was cooler than the rest of the extremities with gradual improvement in discoloration of his hands over sluggish capillary refill (~3 seconds). The peripheral and next 72-hours. Since there was no evidence of throm- central pulses were equal and regular bilaterally. He was boembolism, his LMWH treatment was discontinued able to move all the extremities without any pain. The after three days and it was decided to follow him closely elevated arm stress test was negative for worsening of in an outpatient clinic without any further medical cyanosis or weakening of the radial pulse, thereby les- intervention. Over the next few months he continued to sening the possibility of thoracic outlet syndrome. He have 1-2 self-resolving episodes of acrocyanosis per was referred to a tertiary pediatric facility where he was month, involving both hands along with bluishness of admitted for further evaluation. tip of the nose, lips, ears and periumbilical area and each lasting for a few minutes to an hour. They were Evaluation during hospitalization not associated with cold exposure but were felt to be Upper extremity duplex ultrasound, MRI/MRA/MRV of precipitated by abdominal colic due to constipation. At head, neck and left upper extremity were performed to 9 months of age his initial tests for SLE, and other rheu- rule out anatomical disturbances in vascular supply. matic diseases was repeated. This evaluation was Each test was negative. These results excluded several normal. conditions, including thromboembolism, thoracic outlet Based on his clinical course, he was diagnosed to have syndrome contributing to compression of subclavian “primary Raynaud’sphenomenon”. His treatment vein, vascular anomalies, and the presence of a mass or included laxatives for constipation and close clinical tumors in the region of cervical plexus including the monitoring. Over the next one year, he continued to stellate ganglion. A transthoracic echocardiogram con- have occasional episodes of acrocyanosis without any firmed normal cardiac anatomy and did not demon- medical consequences. At his last follow up (age 2 strate any intracardiac mass, thrombus, or vegetation to years), his growth and development was normal (length suggest an embolic source for a presumed thrombotic and weight at 90th percentile). event. He underwent blood tests to detect infection and Discussion other systemic causes of acrocyanosis such as methemo- The infant described in this report presented with a uni- globinemia, polycythemia, antiphospholipid antibodies, lateral acrocyanosis at one month of age. He was diag- and other hypercoagulable conditions. The complete nosed to have primary RP at 9 months. This diagnosis blood count and comprehensive metabolic panel were was based on his clinical course and exclusion of other normal. The erythrocyte sedimentation rate (ESR) and causes of unilateral acrocyanosis including vascular C-reactive protein (CRP) tests were also normal. His anomalies, thromboembolism and thoracic outlet syn- newborn screen for inborn errors of metabolism and drome. (Table 1) [7]. Even though acrocyanosis is very hemoglobinopathies was negative. His coagulation tests common condition in newborn period, involvement of (PT and aPTT) were normal and antiphospholipid anti- only one hand was an atypical finding for infantile acro- bodies and antinuclear antibody (ANA) assays were cyanosis. This finding providedacluetoconsiderthe negative. He also underwent testing for inherited throm- possibility of RP in the differential diagnosis. bophilia such as factor V Leiden mutation, prothrombin Over the last decade significant advances have been gene mutation, and methylene tetrahydrofolate reduc- made in understanding the pathophysiology of RP tase (MTHFR) mutation. Results were positive for [17-21]. Irrespective of the underlying etiology, RP is homozygosity for a MTHFR C677T mutation with nor- manifested via vasospasm of the small muscular arteries mal homocysteine levels. and arterioles of the digits [18]. Similar to benign acro- Due to the concerns about the transplacental transfer cyanosis of infancy, RP is also triggered by exposure to of maternal antibodies contributing to development of cold and emotional stress. It can be asymmetric and RP in this young infant, it was decided to evaluate his may last longer than benign acrocyanosis. Based on the mother for other medical conditions associated with RP available data, an over- activity of the sympathetic ner- [14-16]. Her blood work up revealed no evidence for vous system along with an imbalance of vasodilator and systemic lupus erythematosus (antiphospholipid antibo- vasocontrictor substances may be the most likely etiol- dies, ANA, antidsDNA), scleroderma (antitopoisomerase ogy for RP [18]. In patients with RP, digital cutaneous 1 antibodies) or cryoglobulinemia (cryoglobulin levels). neurons show a deficient release of a potent