70-Year-Old-Man with Left-Sided Facial Swelling

A 70-year-old man was admitted to the hospital with sudden onset of left-sided facial erythema and edema. He denied antecedent trauma to the face. Three days before, he noted a small pustule on the internal aspect of his left naris, which drained a small amount of purulent fluid. On the day of admission, he awoke at approximately 3:30 am with a mildly swollen left face. Later that same day, the swelling progressed considerably and his speech became slurred, prompting him to seek medical attention. On admission, he reported having chills, jaw pain, and facial tenderness. He denied fevers, chest pain, shortness of breath, nausea, vomiting, diarrhea, light-headedness, headaches, ear pain, eye pain, changes in vision or hearing, and any sensation of swelling in his throat. Additionally, he denied a history of cough, sinus pressure, or purulent nasal drainage. He was able to swallow his oral secretions.

Review of the medical history revealed recent giant cell arteritis (GCA), diagnosed 2.5 weeks before admission via left temporal artery biopsy. Since that time, the patient had been taking 40 mg/d of prednisone. Notably, he had had a dental abscess of a right mandibular molar (#30) drained 3.5 weeks before admission. He did not have any other recent surgeries or infections of the head or neck.

On examination, the patient was afebrile, alert, oriented, and in no acute distress, with a blood pressure of 156/78 mm Hg and a pulse rate of 92 beats/min. He had substantial, poorly demarcated swelling of the entire left side of the face, extending to the midline. The area was erythematous, edematous, and tender to palpation. No blisters, bullae, vesicles, streaking, or regional lymphadenopathy were detected. The patient preferred to keep his left eye closed but was able to open it. Conjunctivae, extraoculomotor movements, and pupils were normal. A small (4-mm), nonpurulent, ulcerated lesion in the mucosa of the patient's left naris was noted. The incision from the left temporal artery biopsy was well healed and without signs of dehiscence or infection. The oropharynx was unremarkable. No oral lesions, ulcers, glossal edema, or oropharyngeal soft tissue swelling was evident. The neck was supple. Findings on cardiac, lung, and abdominal examinations were unremarkable. No stridor, wheezes, or rales were detected. Cranial nerves II through XII were grossly intact; however, the patient mumbled as a result of the facial swelling.

Initial laboratory testing yielded the following results (reference ranges provided parenthetically): leukocytes, 19.7 × 10⁹/L (3.5-10.5 × 10⁹/L); neutrophils, 18.2 × 10⁹/L (1.7-7.0 × 10⁹/L); hemoglobin, 15.2 g/dL (13.5-17.5 g/dL); platelets, 235 × 10⁹/L (150-450 × 10⁹/L); serum sodium, 137 mEq/L (135-145 mEq/L); potassium, 3.4 mmol/L (3.6-4.8 mmol/L); chloride, 98 mmol/L (100-108 mmol/L); bicarbonate, 31 mEq/L (22-29 mEq/L); blood urea nitrogen, 28 mg/dL (8-24 mg/dL); and creatinine, 1.0 mg/dL (0.9-1.4 mg/dL). Computed tomography of the head demonstrated inflammatory soft tissue stranding adjacent to the left mandible and extending to the level of the left zygoma. No evidence of orbital cellulitis was found.

1. Which one of the following is the most likely cause of this patient's facial swelling?

   1. GCA

   2. Sinusitis

   3. Ludwig angina

   4. Bacterial skin infection

   5. Ramsay-Hunt syndrome

   Giant cell arteritis (GCA) is an inflammatory disorder of the arteries, particularly the aortic arch and its branches, such as the extracranial vertebral arteries and superficial temporal arteries.¹ Despite the recent diagnosis of GCA, the patient's sudden facial swelling is not one of the typical presenting symptoms of GCA. It typically presents with fever, new-onset headache, and visual changes such as diplopia or amaurosis fugax. The absence of these symptoms excluded GCA from our differential diagnosis. Sinusitis, an inflammation of the paranasal sinuses that can present with facial tenderness, generally does not present with extreme facial swelling. Furthermore, this patient denied headache or upper respiratory infection (URI) symptoms, which are hallmarks of acute sinusitis.

   Initially, a mouth infection such as Ludwig angina was considered for this patient, particularly because of his recent dental abscess. Ludwig angina is a potentially life-threatening cellulitic infection of the tissues of the floor of the mouth that can lead to airway compromise. The source of infection is generally from infected lower third molars. The symptoms include neck pain, erythema, edema, “board-like” swelling of the tissues of the submandibular and sublingual spaces, fever, and dysphagia. If left untreated, the cellulitis can progress to involve an entire side of the head.² Fortunately, our patient did not have the oral or computed tomographic findings associated with Ludwig angina.

   A bacterial skin infection of the face can cause sudden facial swelling and was the most likely diagnosis. Other common features of bacterial skin infections include tenderness, erythema, and warmth, all of which were presenting symptoms of this patient. Bacterial skin infections often occur after a break in the skin, but on the face they may be odontogenic in origin. The skin and perhaps the mouth (ie, the dental abscess) of this patient provided several potential portals of entry for bacteria.

   On the basis of findings on history and examination, Ramsay-Hunt syndrome, a sudden facial paralysis occurring with herpetic lesions of the ear, was unlikely in this patient. He had risk factors for developing Ramsay-Hunt syndrome, including older age, high likelihood of prior contact with varicella-zoster virus, and administration of corticosteroids. However, he was not experiencing any ear pain, tinnitus, vertigo, facial paralysis, or herpetic lesions that would suggest Ramsay-Hunt syndrome.

   The portal of entry and depth of bacterial infection were still in question. The care team thought that the infection had most likely entered through a break in the skin, but dental or bony involvement were not ruled out. The Oral and Maxillofacial Surgery service was consulted and noted no dental abscesses on reinspection of the patient's oral cavity. Panorex radiography of the patient's upper and lower jaws, teeth, temporomandibular joints, and sinuses revealed no periapical radiolucencies or interosseous lesions. Thus, findings on radiography were officially summarized as grossly unremarkable. After a bony source of infection was ruled out, ultrasonography of the left side of the patient's face was performed and showed no underlying abscess. Empiric antibiotic therapy, which had been initiated in the emergency department for the patient's presumed skin infection, was continued.

2. Which one of the following infections is the most likely type of bacterial skin infection in this patient?

   1. Erysipelas

   2. Cellulitis

   3. Necrotizing fasciitis

   4. Lymphangitis

   5. Folliculitis

   Erysipelas is a superficial bacterial skin infection of the dermis that classically occurs on the face. It is characterized by a sharply demarcated, erythematous skin lesion that has raised margins and is shiny red, tender, warm, and tense. The lesion is often preceded by fever, chills, and malaise. Erysipelas infections, which enter the skin through minor trauma, surgical incisions, and ulcers, often originate from bacteria in the host's nasopharynx. The infection rapidly invades and spreads through lymphatic vessels. Although the patient's facial lesion had many features suggestive of erysipelas, it did not have sharp, raised borders, making erysipelas less likely. The presentation of cellulitis is similar to that of erysipelas, except that it does not have sharply demarcated palpable margins. Thus, cellulitis was the most likely cause of this patient's facial swelling. Cellulitis differs from erysipelas in that it involves the deeper dermis and subcutaneous fat. It is caused by similar bacteria that enter through breaks in the skin and lead to a warm, erythematous, edematous, tender lesion of the skin and subcutaneous tissues.

   Necrotizing fasciitis is a rapidly spreading infection of the deep fascia with secondary necrosis of subcutaneous tissues. Although the lesion in necrotizing fasciitis can, like this patient's lesion, present with rapidly progressive erythema, it soon becomes dusky in color and shows signs of underlying tissue death. There is also frequent putrid discharge secondary to necrosis, severe pain, subcutaneous air (when gas-producing organisms are involved), and/or a general lack of classic signs of tissue inflammation.³ This was clearly not the case with our patient.

   The patient had no signs of lymphangitis, an inflammation of lymphatic channels that occurs as a result of infection at a site distal to the channel, usually through a break in the skin. It presents with erythematous and irregular linear streaks on the skin, which are often warm and tender and extend from the primary site of infection to draining regional lymph nodes. Of note, in the absence of appropriate antibiotic therapy, cellulitis may be a cause of lymphangitis if the inciting cellulitic pathogen enters local lymphatics. Folliculitis is an infection of hair follicles, usually by a skin bacterium, which leads to inflammation of the follicle, giving the appearance of small, white-headed pimples. Although it can sometimes present with a rash, it does not typically occur on the face and does not lead to the kind of massive facial swelling found in our patient.

   Cultures obtained from swabs of the patient's left naris lesion and left temporal artery biopsy site grew out coagulase-negative Staphylococcus species (likely representing normal, nonpathogenic skin and mucosal flora). Blood cultures were negative.

3. Which one of the following organisms is most likely to have been the causative agent of the patient's facial cellulitis?

   1. Actinomyces israelii

   2. Haemophilus influenzae

   3. Staphylococcus aureus

   4. Pseudomonas aeruginosa

   5. Group B Streptococcus

   A israelii is a gram-positive, anaerobic bacillus that generally resides in the oropharynx, as well as in dental plaques and caries. It is the causative agent of actinomycosis, including cervicofacial actinomycosis and Ludwig angina. Cervicofacial actinomycosis can occur in the setting of periodontal disease and is characterized by a (typically) painless swelling of the perimandibular region, followed by the formation of multiple draining fistulae that discharge pus containing yellow sulfur granules.⁴ Our patient did not have any draining sinus tracts in his oral cavity suggestive of cervicofacial actinomycosis, nor did he have Ludwig angina.

   H influenzae is an opportunistic gram-negative coccobacillus of the respiratory tract that is divided into encapsulated and nonencapsulated strains. The former are more virulent and can cause invasive disease such as cellulitis and meningitis; the latter generally cause mucosal infections such as otitis media, bronchitis, and pneumonia. The cellulitis caused by invasive Haemophilus species can occur in the buccal region, leading to extensive facial swelling; however, this cellulitis is usually preceded by a URI and almost exclusively occurs in childhood.⁵ Our patient was an elderly man who denied recent URI symptoms, making it unlikely that the infection was caused by Haemophilus species.

   S aureus, a gram-positive bacterium that normally resides on the skin, is one of the most common etiologic agents of cellulitis and is the most likely cause of our patient's facial cellulitis. The presence of a contiguous purulent nasal lesion is a clue that S aureus should be suspected. P aeruginosa is an opportunistic gram-negative bacillus residing in moist environments that can cause a variety of infections in humans, including pneumonia, urinary tract infections, and meningitis. However, Pseudomonas species do not generally grow on dry skin and almost never cause facial cellulitis, except occasionally in severely neutropenic patients.⁶

   Group B Streptococcus, a gram-positive bacterium that colonizes the vaginal and gastrointestinal tracts in women, has only been defined as a serious pathogen in nonpregnant adults in the past 30 years. It is a very rare source of infection in healthy individuals and is almost always associated with an underlying comorbid condition, such as diabetes, infection with human immunodeficiency virus, chronic heart failure, renal dysfunction, or liver disease (none of which our patient had).⁷ Although group B Streptococcus can cause cellulitis, it does so much less frequently than S aureus or group A Streptococcus, another extremely common cause of cellulitis.

   During the next 24 hours, the patient's facial swelling improved only modestly, remaining erythematous, warm, and mildly tender. However, he remained afebrile and his white blood cell count began to decrease.

4. Which one of the following is least likely to have been a predisposing factor for the patient's condition?

   Corticosteroid use

   Age

   Right dental abscess

   Left temporal artery biopsy

   Left naris lesion

   Our patient possessed several risk factors for developing facial cellulitis. First, he had been taking prednisone before admission; immunosuppressive medications can make a patient more susceptible to skin infections.⁸ Second, his advanced age was a risk because adults older than 50 years are more commonly affected.⁹ A dental abscess is another potential portal of entry for cellulitic pathogens; however, the patient did not have any dental abscesses at presentation, and the one drained 3.5 weeks before admission was on the lower right side of the mouth. It is unlikely that this previous right-sided dental abscess would have caused his left-sided facial cellulitis. Although the left temporal artery biopsy site was clean and dry, it was a break in the skin and located on the side of the face with the erythema, making it a possible portal of entry. Finally, the patient had several visible breaks in his nasal mucosae and facial skin that could have allowed cellulitis-causing organisms to enter, increasing his chance of developing left-sided facial cellulitis. Notably, other risk factors for developing cellulitis include chronic lymphedema and intravenous drug use.

   After 48 hours, the patient had not adequately responded to clindamycin and ceftriaxone. The left side of his face was still markedly swollen and painful. However, he had not developed any systemic symptoms of infection, and his leukocyte count decreased to 14.6 × 10⁹/L. Because of the poor response to this antibiotic regimen, the care team decided to change antibiotics.

5. Given the patient's failure to respond to the initial antibiotic treatment regimen, which one of the following is the most appropriate next antibiotic treatment regimen for this patient's condition?

   1. Cephalexin

   2. Dicloxacillin

   3. Vancomycin

   4. Cefepime

   5. Meropenem

   Cephalexin, a first-generation cephalosporin, is a relatively broad-spectrum antibiotic that has excellent gram-positive coverage. It is particularly effective in the treatment of skin infections caused by group A Streptococcus and S aureus and is considered a first-line agent for the treatment of cellulitis. The patient had already failed to respond to ceftriaxone, a third-generation cephalosporin with broader coverage and similar activity against Streptococcus and Staphylococcus species. Ceftriaxone also has greater efficacy against resistant organisms, but like cephalexin, it does not have activity against methicillin-resistant S aureus (MRSA). Unfortunately, MRSA has become a much more common cause of cellulitis, even in the community.¹⁰ The patient's poor response suggested that he might be infected with a resistant organism such as MRSA. Dicloxacillin, a narrow-spectrum β-lactam that does not have activity against MRSA, would also not be an appropriate choice for this patient, despite the fact that it is often an effective treatment for cellulitis caused by certain forms of resistant S aureus (other than MRSA).

   The team chose to initiate vancomycin therapy to treat a potential MRSA infection. Neither cefepime nor meropenem is active against MRSA, and neither was considered as a single agent in this case. During the next 24 hours, the patient showed dramatic response to the new regimen. A peripherally inserted central catheter was placed, and he successfully completed a 2-week course of antibiotics as an outpatient.

DISCUSSION

Sudden, unilateral facial swelling has a relatively narrow differential diagnosis but includes a few potentially life-threatening conditions. These include cervicofacial actinomycosis, necrotizing fasciitis, and Ludwig angina.⁹ Any oral or facial trauma should be assessed, and attention should be focused on the patient's dental history. A thorough examination of the facial skin as well as the oral cavity and nasopharynx must be performed to identify any potential portals of entry for microorganisms. Computed tomography, Panorex radiography, and ultrasonography may be useful early diagnostic tools to help detect bony abnormalities or soft tissue masses.

Cellulitis was determined to be the cause of acute, unilateral, facial swelling in this patient, after more serious conditions were ruled out. Cellulitis is an inflammatory condition of the dermis and subcutaneous tissues resulting from an invasion of microorganisms through a breach in the skin's protective barrier. Cellulitis appears as a warm, red, swollen, tender, expanding lesion with poorly demarcated, nonpalpable borders (a distinguishing feature from erysipelas) that spreads rapidly through the entire layer of the skin. Untreated, cellulitis may also lead to infection of other surrounding tissues, including the blood vessels, lymphatics, or (rarely) the deep fascial lining, causing bacteremia, ascending lymphangitis, or necrotizing fasciitis, respectively.

Although most common on the legs,¹¹ cellulitis can occur anywhere on the body, including the face. Risk factors for developing cellulitis include old age, intravenous drug use, lymphedema, immunosuppression, and any disruption in the skin surface. Most cellulitis infections are caused by bacteria, with the most common pathogens being S aureus and group A Streptococcus. Treatment regimens are generally targeted at these bacteria, even when cultures are unrevealing. Commonly used antibiotics are cephalexin, dicloxacillin, ceftriaxone, and clindamycin; however, because of the rising incidence of MRSA infections, vancomycin must be considered in the treatment of all hospital- and community-acquired cellulitis infections that do not respond to first-line therapeutic agents. Rarely, bacteria such as Pseudomonas species, Haemophilus species, Streptococcus pneumoniae, or an enterobacterium may be the etiologic agent of a cellulitis infection.^11,12 These organisms should be considered in patients who do not respond to standard empirical therapy; in such cases, antibiotic coverage should be broadened to target these organisms.

Correct answers: 1. d, 2. b, 3. c, 4. c, 5. c.