The Physician and Sportsmedicine
Menubar About Us [Advertiser Services] CME Resource Center Personal Health Journal Home

Facial Injuries in Sports

A Team Physician's Guide to Diagnosis and Treatment

Samuel J. Romeo, MD; Christopher J. Hawley, MD; Michael W. Romeo, MD; Joseph P. Romeo, MD

Practice Essentials Series Editors:
Kimberly G. Harmon, MD; Aaron Rubin, MD


For CME accreditation information, instructions and learning objectives, click here.

In Brief: Team physicians must be prepared to manage facial injuries, including contusions, abrasions, lacerations, nasal fractures, septal hematomas, auricular hematomas, ruptured tympanic membranes, and fractures of the facial bones. With a focused history and a thorough physical exam, the diagnosis can be clearly established. Early treatment of sports-related facial injuries helps avoid complications, and athletes may expect to return to play after predictable time intervals.

Few sports mandate the use of face masks or mouth guards, so faces are usually exposed and susceptible to injury during participation. Sports activities account for 3% to 29% of all facial injuries and approximately 10% to 42% of all facial fractures.1-7 Depending on the clinical setting, approximately 60% to 90% of these injuries occur in male participants between 10 and 29 years old.4-9 In 1995, more than half the children under age 11 who were injured while playing baseball sustained injuries to the head or neck.10

The mechanism of injury is often direct impact with another player's body part (eg, head, fist, elbow), equipment (eg, ball, puck, goalpost, handlebars), the ground (eg, wrestling mat, gym floor), or the environment (eg, tree on a ski slope, outfield wall in baseball).6,11 Injury patterns vary by sport, but facial injuries in soccer, rugby, baseball, boxing, and skiing are common.3,6,7,9,10 Treatment requires knowledge of the many types of facial injuries. Return-to-play decisions are individualized based on the type and severity of injury and the physical demands of the sport.

Initial Exam and Evaluation

Because the head and neck have a rich blood supply, injuries in this area are notorious for brisk bleeding. The examiner must always remember that the "wow factor" associated with profusely bleeding traumatic injuries should never detract from a systematic evaluation. All head and neck injuries should be treated initially as closed head injuries. Initial assessments should include an evaluation of the patient's airway, breathing, and circulation status.

The airway is particularly vulnerable to obstruction with head and neck injuries because of bleeding, structural compromise of bony structures (eg, the mandible), or dislodged teeth, tooth fragments, or dental appliances. Cervical spine precautions should be taken when symptoms of neurologic deficits or cervical-spine tenderness are present and with all unconscious athletes. The patient should be removed from the field, court, or track as quickly as possible without compromising safety. If the athlete is conscious, the clinician can obtain the athlete's medical history while applying direct pressure to bleeding areas with gauze.

Pertinent history. The mechanism of injury should be ascertained, and the source of the athlete's pain should be located. Signs or symptoms of blurred vision, diplopia, concussion, or cerebrospinal compromise should be evaluated. Identifying what protective gear the athlete was wearing, such as a face mask, mouth guard, or throat guard, may provide information about the injury site.

Physical exam. Immediate attention should focus on: (1) identifying areas of ecchymosis, edema, or active bleeding; (2) inspecting the nasal septum and external ears for hematomas; (3) looking for a sunken eye globe suggestive of a blowout fracture; and (4) observing lacerations or deep abrasions overlying suspected fractures. Early recognition of facial asymmetry or structural depressions—before edema distorts the overlying soft tissue—is critical to early clinical diagnosis of facial fractures.

Systematic palpation of the facial bones (eg, orbital rims, nasal bones, and temporomandibular joints) will reveal significant tenderness, crepitus, numbness, or contour irregularities. Midface instability or crepitus may be demonstrated by stabilizing the forehead with one hand while gently pulling on the maxillary incisors with the other gloved hand. Bimanual palpation along the mandible and maxilla (one gloved hand palpating intraorally) will uncover instability, irregularity, or tenderness.

Extraocular eye movements and cranial nerves III, IV, and VI can be assessed by having the patient keep his or her chin in a fixed position while tracking the examiner's finger movements in all four quadrants. If the patient is able to track the movements without reporting diplopia, acute extraocular muscle entrapment caused by an orbital blowout fracture can be ruled out (see "Facial Trauma in a Softball Player").

Lacerations or fractures can injure the facial nerve (ie, cranial nerve VII) or one of its branches; therefore, facial symmetry should be assessed (table 1). Injured athletes should be instructed to open and close their mouths. If they are unable to open, if they exhibit trismus, or if they experience severe pain along the lateral aspect of a cheek or jaw when attempting to open, a fracture of the mandible or zygoma must be considered. With the mouth open, the oral cavity should be assessed to rule out damage to the teeth and lacerations in the intraoral mucosa or tongue. Fractured or missing teeth should be located, when possible, to avoid accidental aspiration. When asked to close their mouths, the patients' sense of malocclusion strongly suggests a significant fracture of the mandible, maxilla, or palate.

TABLE 1. Physical Examination of Cranial Nerve VII

MovementInnervated By
Raise the eyebrows  Temporal branch
Close eyes tightlyZygomatic branch with some cross-innervation from the buccal branch
Smile (wide)Forehead: temporal branch
Midface: buccal branch with cross-innervation from zygomatic branch
Corner of mouth: marginal mandibular branch
Open mouth wide
or pucker lips
Marginal mandibular branch

Tests. A patient who has a cerebrospinal fluid leak related to a fracture of the cribriform plate may report a salty taste in the mouth. A ring test is used to confirm a cerebrospinal fluid leak in a stable patient. The patient sits with the neck in flexion while a drop of nasal blood is collected on a piece of gauze. The test is positive if a clear fluid ring forms around the blood on the gauze within seconds.

Although it is not necessary for most nasal fractures, a plain radiograph facial series may be indicated if other fractures involving the mandible, zygoma, or zygomatic arch are suspected. Panorama views should be included to assess the mandible. When readily available, computed tomography is extremely sensitive for detecting bony abnormalities of the face and is commonly used in evaluating suspected fractures of the facial bones.

Soft-Tissue Injuries

The facial skin and underlying soft tissues are vulnerable to damage and disruption, especially if the athlete is not wearing protective gear. Sideline medical personnel are often called upon to manage contusions, abrasions, and lacerations.

Contusions are the most commonly encountered facial injury, and they usually result from blunt trauma to the face. Treatment is aimed at minimizing the immediate inflammatory response. Ice should be applied for 20 minutes at a time, several times per day, for the first 48 hours after initial injury. Nonsteroidal anti-inflammatory drugs may be considered for early pain management. Athletes may return to play immediately if no visual obstruction is caused by edema and if no other warning signs are present. Complications are uncommon but may include a large, persistent, painful, or disfiguring hematoma that requires surgical evacuation.

Abrasions, or partial-thickness disruptions of the epidermis, commonly result from blunt trauma or sudden forcible friction along the face. The prominent structures of the face (eg, nose, cheek, eyebrow, chin) are more prone to abrasion. As with all soft-tissue injuries, underlying injury must be ruled out.

More than 40% of all reported cases of tetanus between 192021 and 2021 resulted from abrasions and lacerations; therefore, tetanus immunization status and subsequent wound management are important considerations with all open wounds12,13 (see "Sideline Care of Abrasions and Lacerations: Preparation Is Key").

Treatment of abrasions requires gently cleansing the skin of all debris. If the athlete is unable to tolerate primary debridement without pain control, a 4% lidocaine hydrochloride solution can be topically applied or a regional infiltrative block can be used. Occasionally, wounds require extensive cleaning and secondary debridement, and these patients should be referred to the appropriate setting (eg, emergency department, urgent care, outpatient clinic, surgery center) for management. "Tattooing" can occur when foreign debris is left in an abrasion. This gives the skin an irregular hyperpigmentation and can lead to a poor cosmetic outcome. Secondary infections of facial abrasions are rare, because the face has a rich blood supply.

Lubricating the wound with antibiotic ointment and covering it with a sterile dressing encourages healing. In addition, athletes should be instructed on basic wound care. When possible, abrasions should be covered with the appropriate bandage, and athletes may return to competition at their discretion. In sports such as basketball, covering bloody wounds is mandatory before returning to competition; in sports such as boxing, definitive management and wound care are initiated at the conclusion of the contest.

Lacerations are common in sports and vary widely in complexity. Initial attention should focus on hemostasis with direct pressure. Definitive treatment includes irrigation and conservative debridement when necessary. All lacerations requiring sutures should be closed as soon as possible. Lacerations older than 12 hours should not be sutured but rather be allowed to heal by secondary intention, because of the increased risk of wound infection. Tongue lacerations heal extremely well and rarely require sutures.

Lacerations with any of the following characteristics are at high risk for poor cosmetic or functional outcomes and should be definitively managed in an appropriate setting:

  • Large tissue deficits or irregular edges requiring debridement and possibly a skin graft;
  • Significant disruption of the lip vermilion border;
  • Large through-and-through lacerations of the cheek or lip that may require approximation of the underlying musculature;
  • Facial nerve deficits;
  • Ear or nose cartilage injuries that have poor blood supply and are prone to secondary infections and chondritis;
  • Suspicion of an underlying fracture;
  • Any deep laceration that may involve the parotid duct, which generally courses along an imaginary line from the tragus to the maxillary second molar; or
  • Involvement of the eyelid or lacrimal duct.

Emergent referrals for head and neck surgery, plastic surgery, or ophthalmology should be considered.

An athlete who has a superficial laceration can return to activity immediately if the wound is protected. Deep lacerations require complex closure after the surrounding structures (eg, nerves, glands) are identified. Athletes who require more complex laceration repairs generally return to play in 5 to 21 days, depending on the deep structures involved. Complications include persistent bleeding with hematoma formation, infection with possible reopening of the wound, and unacceptable scarring.

Nasal Injuries

Because the nose protrudes from the face and because few sports require protective face masks, nasal injuries are extremely common in athletics (see the Patient Adviser, "What to Do for Nasal Injuries"). Injuries range from contusions to fractures and generally result from a direct or glancing blow to the nose. Epistaxis is a common presenting symptom that is easily identified. Most nosebleeds originate from the anterior septum (Kiesselbach's area) and are easily visualized with a nasal speculum (figure 1). Persistent or profuse bleeding may indicate a complex nasal fracture with an injury to the ethmoid artery that requires direct visualization. Posterior epistaxis is usually atraumatic and would be rarely encountered by physicians on the sidelines.

Athletes who sustain a nasal fracture frequently report having heard a "crunch" or "crack," described as the sound of biting into uncooked macaroni. Blows to the cartilaginous complex frequently cause septal fractures and dislocations; lateral blows often displace the nasal bones.14 Nasal fractures are diagnosed clinically, and imaging studies are generally not needed. Recognizing a deformity before the rapid onset of edema is key to a good outcome.

If patients arrive after swelling has already begun and their only injury is to the nose, we evaluate them to ensure they do not have a septal hematoma (ie, blood from an acute injury that accumulates beneath the septal perichondrium) that would require incision and drainage. If a septal hematoma is ruled out, they are instructed to return in 3 to 5 days for a follow-up evaluation.

The focus of initial treatment is on hemostasis and minimizing swelling. Treatment of nasal fractures includes ice, pain control (aspirin is contraindicated because of its blood-thinning properties), and nasal decongestants or saline spray for up to 3 days. Displaced nasal fractures should either be reduced immediately (within the first hour) or referred to a head and neck surgeon for reduction when swelling has decreased, approximately 3 to 5 days later.

Anterior epistaxis is best controlled by slightly reclining the patient and applying direct pressure to the nasal septum for 5 to 10 minutes. Applying ice to the back of the neck may assist by causing reflex vasoconstriction. Persistent epistaxis occasionally requires nasal packing with a Merocel sponge (Medtronic Inc, Xomed, Jacksonville, FL) covered in topical antibiotic or a topical coagulant (such as FloSeal, Fusion Medical Technologies, Mountain View, CA). Phenylephrine hydrochloride or oxymetazoline hydrochloride may also be used to cause vasoconstriction.

Return to play from a nasal fracture can be immediate if bleeding is controlled. Custom acrylic face shields, helmets with face masks, or other protective devices should be worn during contact sports for 4 weeks after injury.15 In noncontact sports, such as cross-country running, athletes may return to competition immediately if hemostasis is maintained.

Complications from nasal fractures include chronic nasal obstruction, deviated septum, and septal hematoma.16 When an athlete sustains a nasal contusion or fracture, it is imperative to rule out a septal hematoma, a bulging bluish septal mass (figure 2) that requires prompt surgical drainage, nasal packing, and prophylactic antibiotics. Septal hematomas generally form within hours after the injury. Diagnosis and treatment of septal hematomas ideally occur on the initial day of injury, but complication rates are low if treatment is initiated at the first follow-up visit for fracture re-evaluation. Failure to drain the mass can lead to infection or pressure necrosis of the underlying bone and cartilage. If necrosis occurs, the septum can collapse, resulting in an extremely poor cosmetic appearance known as a saddle nose.

Ear Injuries

Contusions caused by shearing forces applied to the external ear are common in sports, most notably in wrestling, in which the mechanism of injury is blunt trauma against a wrestling mat. The diagnosis is easily established by ecchymosis, erythema, and pain.

Auricular hematoma. A patient who has an auricular hematoma usually exhibits palpable collections of fluid that are painful and throbbing. Swelling of the external ear with loss of anatomic landmarks, such as the helix and antihelix, often occurs (figure 3). The athlete will report severe pain that may not appear consistent with the clinical signs.

Ice applied with continuous compression for 20 minutes at a time can minimize the risk of developing an auricular hematoma. Treatment consists of prompt aspiration of the hematoma with a 20-gauge needle or incision at the inferior border and drainage using sterile technique. To avoid reaccumulation of blood, compression should be applied for 7 to 14 days. Compression may be obtained by (1) applying dental rolls, nonadherent bandages, or a button to the anterior and posterior surfaces of the ear and fixing them in place with through-and-through sutures; (2) applying fine gauze to the anterior and posterior surfaces and then layers of collodion; or (3) applying a silicone splint molded to the anterior and posterior aspect of the ear and suturing it in place (figure 4).17

Athletes who participate in noncontact sports may return to play immediately. Ear protection, such as headgear or a helmet, is needed for immediate return to contact sports. If sutures were placed to hold the dental rolls or buttons for compression, contact sports may be resumed approximately 24 to 48 hours after sutures are removed. Prophylactic use of antibiotics such as cephalosporins is recommended for 7 to 10 days.

Auricular hematomas, like septal hematomas, can result in severe cosmetic deformities. A hematoma can cause pressure necrosis of the underlying cartilage by separating the perichondrial blood supply from the underlying cartilage, resulting in a cauliflower ear.

Perforated tympanic membrane. Pressure created by otitis media remains the most common cause of perforated tympanic membranes, but sports-related blunt trauma or barotrauma from swimming, diving, or altitude changes can cause the injury. An athlete may be asymptomatic or report symptoms such as hearing loss, vertigo, bloody or serous discharge, or discomfort in the ear worsened by wind or cold weather. An otoscope will allow visualization of a defect in the membrane. The compromised tympanic membrane will not move with a puff of air from a pneumatic bulb. Small defects in the membrane (less than 2 mm) will often heal spontaneously within weeks.18

The ear canal should be kept dry, and ototopical antibiotics are recommended to prevent complications.19 In sports where significant pressure changes occur, such as platform diving, scuba diving, and highaltitude mountain climbing, athletes should not return to play until the membrane has healed. Athletes participating in water sports, such as swimming and water polo, should use custom-fabricated ear plugs to ensure a dry ear canal. Dry-land athletes may return to play as soon as any vertigo has resolved.

Fractures and Dislocations

Although one would expect variation depending on the sport played, nearly 75% of facial fractures occur in the mandible, zygoma, and nose.5 A standard, thorough physical exam is designed to clinically detect facial fractures and dislocations and guide management decisions (table 2). Early recognition is the key to appropriate management of facial fractures.

TABLE 2. Diagnosis and Treatment of the Most Common Facial Fractures

TypeMechanism of InjuryCharacteristic Signs and SymptomsDiagnostic Imaging  Usual Definitive TreatmentReturn to Play
MandibleTrauma to lower faceMalocclusion; abnormal
mandibular movement
Plain film with
panorama view
or CT
Nondisplaced closed fracture (usually
two sites): treatment with fixation

Displaced, unstable, complex, or open
fracture: open reduction and internal fixation
Noncontact: as tolerated
Contact: 6 wk

6-8 wk
Blunt trauma to cheekPain, swelling; ecchymosis over fracture
site; numbness along infraorbital nerve
(upper lip or cheek); depressed malar
eminence and inferior orbital rim
Water's view and
submental vertex
view radiograph
or CT
Nondisplaced closed fracture: conservative
treatment with observation

Displaced, unstable, complex, or depressed
fragment: open reduction and internal fixation
Noncontact: as tolerated
Contact: as tolerated with face guard

4 wk
NasalDirect or glancing blowHeard "crack"; ecchymosis; tearing;
epistaxis; crepitus
NoneNondisplaced closed fracture: conservative
treatment with observation

Displaced: closed reduction

Comminuted: possible open reduction
Noncontact: when bleeding is controlled
Contact: when bleeding is controlled; requires face guard

1-2 wk with face guard

1-2 wk with face guard
Blunt trauma to cheekCentral depression or asymmetry of cheek  
bone; trismus caused by impingement of
the arch on the coronoid process of the
mandible or temporalis muscle
Submental vertex
view radiograph
or CT
Nondisplaced closed fracture: conservative
treatment with observation

Displaced, unstable, complex, or depressed
fragment: open reduction, rarely with internal
Noncontact: as tolerated
Contact: 2 wk with face guard

1-2 wk postoperative with face guard
Maxilla or
Le Fort's
High-velocity shearing force  
to midface (eg, bat,
baseball, or hockey puck to
face; motocross accident)
Elongated, distorted face; mobile maxilla
with bimanual exam; malocclusion
CTNondisplaced closed fracture: conservative
treatment with observation

Displaced, unstable, complex, or depressed
fragment: open reduction and internal fixation
3-4 wk with face guard

Depends on fracture characteristics
Direct trauma to globe
(eg, from ball, elbow)
Periorbital edema; ecchymosis;
subconjunctival hemorrhage;
numbness along infraorbital nerve (upper
lip or cheek); limitation of upward gaze
resulting from entrapment of the inferior
rectus and superior oblique extraocular
muscles; diplopia; sunken globe
CTNondisplaced closed fracture: conservative
treatment with observation

No entrapment of extraocular muscles: close
observation to ensure entrapment does not occur

Entrapment of extraocular muscles: open
reduction and internal fixation
Minimum 4-6 wk

Depends on fracture characteristics

Varies widely; depends on fracture characteristics

Particular attention should be paid to facial symmetry before edema sets in and distorts the soft tissue in the nose, orbital rims, zygomatic arches, maxilla, and mandible. Deficits in symmetric eye movements suggest extraocular muscle entrapment or an orbital blowout fracture. The athlete's sense of malocclusion or reduced mandible movement is sensitive for detecting fractures of the mandible or maxilla. On-site intervention may be warranted in two circumstances: a displaced, closed nasal fracture or a dislocated mandible without fracture.

Reduction of a deviated septum may be attempted in the first hour after injury by using gentle pressure with a soft probe inside the nares to elevate the depressed or displaced septum into anatomic position. Nasal splinting is often used to prevent drifting of the reduced fracture. An inability to stop nose bleeding may indicate a more serious problem, such as a complex nasoethmoid fracture and damage to the ethmoid artery. This type of fracture can be associated with a cerebrospinal fluid leak and should be evaluated in an appropriate setting where emergent care can be given.

Dislocation of the mandible occurs with traumatic depression. Malocclusion and mandibular deviation away from the dislocated condyle is notable on physical exam. Care must be taken to distinguish between a mandibular dislocation and a displaced fracture of the condyle. The dislocated mandibular head will reside anteriorly to the articular eminence of the glenoid fossa. Mandibular relocation can often be accomplished without sedation shortly after the injury and before severe facial muscle spasm and edema develop. With the patient in a sitting position, the physician should place one hand on each mandibular condyle and apply steady downward and then posterior traction. The traction will allow the condyle to slip back into position in the glenoid fossa. Open fractures require prompt surgical management.

Facing the Competition

A thorough history and a methodical physical exam improve diagnostic accuracy, allow for early initiation of treatment, and reduce the time that athletes must spend on the sidelines. Return-to-play recommendations vary based on the demands of the athlete's sport and the specific characteristics of the injury, such as location, extent, and potential complications. Appropriate facial protection (eg, face masks in football or acrylic face shields commonly used in basketball for nasal fractures) can reduce the risk of injury and accelerate return to play.

While prevention remains the primary goal, clinicians must be prepared for evaluating facial injuries. Accurate diagnosis, prompt treatment, and appropriate referrals to specialists will allow athletes the best opportunity for a safe and predictable return to activity.


  1. Beck RA, Blakeslee DB: The changing picture of facial fractures: 5-year review. Arch Otolaryngol Head Neck Surg 120219;115(7):826-829
  2. Linn EW, Vrijhoef MM, de Wijn JR, et al: Facial injuries sustained during sports and games. J Maxillofac Surg 120216;14(2):83-88
  3. Frenguelli A, Ruscito P, Bicciolo G, et al: Head and neck trauma in sporting activities: review of 208 cases. J Craniomaxillofac Surg 1991;19(4):178-181
  4. Muraoka M, Nakai Y: Twenty years of statistics and observation of facial bone fracture. Acta Otolaryngol Suppl 192021;538:261-265
  5. Iida S, Kogo M, Sugiura T, et al: Retrospective analysis of 1502 patients with facial fractures. Int J Oral Maxillofac Surg 2021;30(4):286-290
  6. Tanaka N, Hayashi S, Amagasa T, et al: Maxillofacial fractures sustained during sports. J Oral Maxillofac Surg 1996;54(6):715-719
  7. Maladiere E, Bado F, Meningaud JP, et al: Aetiology and incidence of facial fractures sustained during sports: a prospective study of 140 patients. Int J Oral Maxillofac Surg 2021;30(4):291-295
  8. Perkins SW, Dayan SH, Sklarew EC, et al: The incidence of sports-related facial trauma in children. Ear Nose Throat J 2021;79(8):632-638
  9. Fasola AO, Obiechina AE, Arotiba JT: Sports related maxillofacial fractures in 77 Nigerian patients. Afr J Med Med Sci 2021;29(3-4):215-217
  10. CPSC releases study of protective equipment for baseball, release #96-140. US Consumer Product Safety Commission, June 4, 1996. Available at Accessed January 7, 2021
  11. Seguin P, Beziat JL, Breton P, et al: Sports and maxillofacial injuries, etiological and clinical aspect apropos of 46 cases: preventive measures [article in French]. Rev Stomatol Chir Maxillofac 120216;87(6):372-375
  12. Pascual FB, McGinley EL, Zanardi LR, et al: Tetanus surveillance—United States, 192021-2021. MMWR Surveill Summ 2021;52(3):1-8
  13. Centers for Disease Control and Prevention: Tetanus, in Epidemiology & Prevention of Vaccine-Preventable Diseases, The Pink Book, ed 8, 2021, chapter 6. Available at Accessed January 26, 2021
  14. Stackhouse T: On-site management of nasal injuries. Phys Sportsmed 192021;26(8):69-74
  15. Heise M, Eufinger H, Rarreck T: Individualized facial protection after fracture management of the nasal bone and zygomatic arch in professional soccer players [in German]. Mund Kiefer Gesichtschir 2021;5(5):320-322
  16. Alvarez H, Osorio J, De Diego JI, et al: Sequelae after nasal septum injuries in children. Auris Nasus Larynx 2021;27(4):339-342
  17. Lane SE, Rhame GL, Wroble RL: A silicone splint for auricular hematoma. Phys Sportsmed 192021;26(9):77-78
  18. Canalis RF, Abemayor E, Shulman J: Blunt and penetrating injuries to the ear and temporal bone, in Canalis RF, Lambert PR (eds): The Ear: Comprehensive Otology. Philadelphia, Lippincott Williams & Wilkins, 2021, pp 785-800
  19. Isaacson JE, Vora NM: Differential diagnosis and treatment of hearing loss. Am Fam Physician 2021;68(6):1125-1132

Dr Samuel Romeo, Dr Hawley, and Dr Michael Romeo are family practice physicians at Romeo Medical Clinic in Turlock, California. They serve as team physicians for California State University, Stanislaus and as directors of sports medicine at the Stanislaus family medicine residency program. Dr Joseph Romeo is a head and neck surgeon in Turlock. Dr Samuel Romeo and Dr Hawley hold certificates of added qualifications in sports medicine. Address correspondence to Samuel J. Romeo, MD, Romeo Medical Clinic, 777 E Hawkeye Ave, Suite 3, Turlock, CA 95380; e-mail to [email protected].

Disclosure information: Drs Romeo, Hawley, Romeo, and Romeo disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.