Cellulitis

A Review of Facial Cellulitis

L a u r a A t z o r i , C a t e r i n a Fe r r e l i a n d N i c o l a A s t e
Dermatology Department, University of Cagliari

Abstract
Cellulitis is a severe inflammation of the dermis and hypodermis sparing the fascial planes due to an acute infection. A sudden erythematooedematous induration with a bluish hue develops within hours, accompanied by fever, general malaise, pain and paraesthesia. Facial involvement has a high risk of complications due to the abundance of sensitive anatomical structures: cavernous sinus thrombosis, cerebral abscess, meningitis, asphyxia, mediastinitis, pneumonia and septicaemia. The main causative agents are Staphylococcus aureus and Streptococcus pyogenes (especially Group A beta-haemolytic S. pyogenes). Sporadic cases due to other Gram-positive bacteria, Gramnegative bacteria and a mixture of both aerobes and anaerobes are reported. The virulence of the germs, but above all predisposing local and general conditions, are critical. Underlying dermatoses or previous infection, trauma, dental pathology and surgical wounds provide portals of entry. Immunosuppression, diabetes and malignancies are major risk factors. Methicillin-resistant strains are an increasing problem. Early recognition and correct treatment with broad-spectrum antibiotics is mandatory to avoid life-threatening complications.

Keywords
Facial cellulitis, acute bacterial infections, head and neck infection, review
Disclosure: The authors have no conflicts of interest to declare. Received: 15 January 2010 Accepted: 19 April 2010 Citation: European Dermatology, 2010;5:617 Correspondence: Laura Atzori, Clinica Dermatologica, Via Ospedale 54, 09124 Cagliari, Italy. E: atzoril@unica.it

Facial cellulitis (FC) is a severe bacterial infection of the soft tissues.15 Early clinical recognition is mandatory to avoid potentially lifethreatening complications. The dermatologist is in a lead position to avoid misdiagnosis. Aetiology is variable, as mainly Gram-positive but also Gram-negative bacilli and a mixture of both types are able to induce the disease.47 At presentation, when faced with the patient, differentiation between very similar entities caused by the same pathogens might be difficult: cellulitis towards erysipelas, abscess, necrotising fasciitis and gangrene (see Table 1). Erysipelas is a milder form of cellulitis confined to the superficial dermis and lymphatics. It is caused by pyogenes, especially Group A beta-haemolytic Streptococcus (GAS).5,8 The term erysipelas has become widely accepted and maintained because of a characteristic unique presentation, consisting of a bright red patch of swelling with typical raised borders, with non-pitting oedema, sharply demarcated from the adjacent normal skin. This step (scalino) sign from Italian literature is absent in cellulitis, where the soft-tissue inflammation is deeper and widespread from the very beginning. In addition, erysipelas may suddenly evolve into frank cellulitis, and lymphatic involvement is severe in all forms of cellulitis. General malaise, fever and chills accompany both erysipelas and more severe cellulitis. Another distinction should be made between cellulitis and abscesses. An abscess is an enclosed collection of necrotic tissue, bacteria and inflammatory cells, known as pus, somewhere in the body.7 Cellulitis

is a widespread inflammatory process involving the dermal and subcutaneous tissues that becomes somewhat constrained by anatomical limits, muscle insertion and aponeurosis. Abscess formation and fistulisation is an evolution or complication of cellulitis, especially when not adequately treated (suppurative stage). Skin necrosis may complicate conventional cellulitis or may occur with distinctive clinical features. Although deep, the involvement of the subcutaneous tissue in cellulitis should not extend through the subcutaneous fat and fascial planes. If it does so, it is likely to be so-called necrotising fasciitis, which indicates a more severe and extensive cellulitis.9 It responds poorly to broad-spectrum antibiotics and requires aggressive surgical treatment (fasciotomy). The skin can change from red-purple to grey at an alarming rate, with violaceous bullae and areas of shiny watery malodorous fluid discharge due to fat necrosis, the ill-defined patch becoming as hard as wood on deep palpation. The term gangrene is also frequently used in association with cellulitis, especially in the form of gas gangrene, which is synonymous with anaerobic cellulitis.4 Gangrene refers to a deep penetrating wound, rapidly leading to necrosis of the soft tissue, primarily due to a loss of blood supply. It sometimes permits the invasion and proliferation of bacteria, especially those able to survive with little or no oxygen, such as the Clostridium family. These ubiquitous Gram-positive bacilli found in soil and bowel flora generate gas. Facial gas gangrene typically occurs on the submandibular region, neck, eyes and orbits.10

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Table 1: Differential Diagnosis of Soft-tissue Bacterial Inflammation
Entity Erysipelas Aetiopathogenesis An acute inflammation of the superficial dermis and lymphatic system caused by pyogenes, especially the group A beta-haemolytic Streptococcus (GAS). Cellulitis A severe, acute deep soft-tissue infection characterised by rapidly spreading erythema that progresses to abscess formation and is usually accompanied by malaise and fever. Clinical Presentation A bright red swelling patch with typical raised borders, indurate peau dorange non-pitting surface, sharply demarcated from the adjacent normal skin. An expanding area of erythema with all sign of inflammation: rubor, calor, dolor, tumour. Borders are ill-defined, with a typical dusky hue. The surface usually breaks in some points with the appearance of vesicles and/or bullae as well as pustules that progress to pus discharge. Abscess An enclosed collection of necrotic tissue, bacteria and inflammatory cells surrounded by a reactive capsule and cell through the walls of nearby healthy tissues. Necrotising fasciitis Rapidly progressive necrosis of subcutaneous fat and fascia, also known as flesh-eating bacteria syndrome. The patient is toxic, with fever, chills, tachycardia, malaise and altered levels of consciousness. Type I: mixed infection of anaerobes plus facultative species such as Streptococci or Enterobacteriacaea. Type II: infection with group A Streptococci. Gangrene Necrosis of deep soft tissue primarily due to a loss of blood supply, sometimes permitting invasion and proliferation of bacteria, especially those able to survive with little or no oxygen, such as the Clostridium family. It often has an abrupt onset following a deep penetrating wound. Erysipeloid An occupational disease caused by Erysipelotrix rhusiopathiae, a Gram-positive rod contaminating dead matter of animal or fish origin. Veterinarians, meat packers and fisherman are frequently exposed to minimal trauma while handling the contaminated material. Clinical features are common to erysipelas and other bacterial cellulitis, but it is usually milder and tends towards self-limitation. Tender dark yellow or brown discoloration of the skin, with serahaematic bullae and patches of necrosis. A mousy smell is common. Crepitus at palpation supports the diagnosis of gas-producing bacteria (gas gangrene). An erythematous painful swelling area with fluctuation and trophic alteration. A thick yellowish pus escapes from the abscess naturally through fistulisation or through medical intervention. A ill-defined red-purple to grey shiny patch with violaceous bullae, ulcers and areas of shiny watery malodorous fluid discharge due to fat necrosis. Deep palpation reveals a wood hardness. The presence of hypo- or anaesthesia suggests deeper nerve involvement.

For a complete picture, although it never occurs on the face, there is another peculiar disease in the cellulitis spectrum called erysipeloid. It is an occupational disease because the causative organism Erysipelothrix rhusiopathiae is a Gram-positive rod contaminating dead matter of animal or fish origin.11 Veterinarians, meat packers and fisherman are frequently exposed to minimal trauma while handling contaminated material. Clinical features are similar to those seen with other bacterial cellulitis, but erysipeloid is usually milder and tends to have a self-limited course.

Concurrent illness (immunocompromisation, HIV, congestive heart failure or renal insufficiency) or complications (such as shock) may increase the risk of death.20

Aetiology and Pathogenesis

The origin of the infection is sometimes difficult to establish because of the efficient and rapid intervention of skin reticular and lymphoid cells against the antecedent bacteria invasion and proliferation. Even a small number of fragmented bacterial antigens, amplified by cytokine and lymphokine release, are responsible for massive neutrophil chemotaxis and skin infiltration, as well as reduction in the number of viable bacteria in the tissues.36 Pathogens are able to produce rising titres of enzymes (streptolysin, deoxyribonuclease B [DNase], hyaluronidase, neuraminidase, phospholipase) degrading the core components of connective tissue the dermal cytoskeleton. Neutrophil degranulation further amplifies anti-DNase activation. The warmth and erythema associated with cellulitis are a direct expression of this dramatic antigenic response. In the more aggressive forms, the release of bacterial toxins (pyrogenic exotoxin A or B), as well as the synergistic effect of different bacterial species such as Staphylococcus aureus and anaerobes, is to be suspected. 6 When Gram-negative bacteria are destroyed, lipopolysaccharide release in the tissue might result in severe vascular injury and necrosis of keratinocytes, sometimes indicated by the term of haemorrhagic cellulitis.21 The main causative agents in adults are S. aureus and Streptococcus pyogenes (especially GAS), but also other group G, B, C and D

Epidemiology
Cellulitis affects individuals rather than causing epidemics. The precise prevalence of the disease is uncertain; however, a 2006 US study revealed an incidence rate of 24.6 cases per 1,000 people/year.12 In a large epidemiological study of a hospitalised population with skin, softtissue, bone and joint infections, 37.3% patients were identified as being affected by cellulitis.13 Involvement of the head and neck is less frequent than lower extremities in adults and the umbilical region in neonates. Facial cellulitis occurs at any age, without a predilection for race or sex, although a higher incidence among males has been suggested in some studies.14 Children are affected at a very young age, usually seven to 10 months.1519 Generally, the disease occurs in patients in good health, although a history of infections is often reported in the weeks before. Association with otitis media is frequent in infants.16 Forms secondary to surgical procedures, accidents or dental pathology are more frequent in adults, while in older people diabetes or malignant disease are to be suspected.15 Mortality is low after appropriate treatment but may occur in neglected cases or when highly virulent organisms are involved.

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Table 2: Exemplification of Maxillofacial Compartment Anatomy After De Vincente-Rodriguez Modifications 28

Periorbital and orbit compartment Periorbital cellulitis involves the eyelid and periocular tissues anterior to the orbital septum. The orbit is a confined pyramidal space bounded by four bony walls: the floor is made up of the maxilla, zygomatic and palatine bones, the roof of the frontal bone and, behind this, the sphenoid lesser wing. The eyeball and its functional muscles are surrounded by a layer of orbital fat, also containing many important neurovascular structures. It is intimately related to the paranasal sinuses as well as the anterior and middle cranial fossae by the fissures and canals. Major ones include: the optic foramen, through which the optic nerve runs back into the brain and the large ophthalmic artery enters the orbit; and the superior orbital fissure, through which large veins, sensory and motor nerves pass. The front of the orbit is covered by the eyelids essentially folds of tissue containing glands and the muscular layer. Superficial compartment Space immediately under the facial skin delimited cranio-caudally by the zygomatic arch and the lower edge of the mandible, covered by the masseter and buccinator muscles, limited posteriorly by the parotid fascia. It contains the Bichats fat pad, the facial nerve, blood vessels and lymph nodes. It communicates medially with the pterygomandibular space through the sigmoid notch. Masticator compartment This comprises several intercommunicating shallow spaces nearby containing the four masticator muscles covered by their aponeurosis: the masseter, the temporal muscle, the external and internal pterygoid muscles. It can be distinguished grossly at superficial and deep levels. The zygomatic arch and angle of the jaw separate the superficial compartments in a superior compartment (temporal lodge). It is limited by the temporal aponeurosis and contains the temporal muscles, adipose tissue, vessels, nerves, lymph nodes and an inferior level housing the masseter and its submasseter space underneath. The deep level, named pterygoidomandibular space, coincides with the pterygoid muscles, which are covered by a prolongation of the superficial cervical aponeurosis (pterygoid fascia) and the ascending mandibular ramus. Parapharyngeal space Extending from the base of the skull to the mediastinum, this space is limited anteriorly by the pharyngeal wall and posterolaterally by the vascular sheath of the neck and the pre-vertebral aponeurosis. It contains very sensitive structures: lymph glands, the internal carotid artery, the internal jugular vein, the sympathetic nerve and the last four cranial pairs. It communicates with the floor of the mouth, vertebral spaces and masticator compartment. Parotid space Paratonsillar space The superficial cervical aponeurosis before the ascending mandibular ramus unfolds the parotid glands. It is a space that also contains lymph nodes, the facial nerve, the external carotid and the retromandibular vein. The palatine tonsils are lodged under the pillars of the palatine vellus, limited posteriorly by the superior constrictor muscle of the pharynx. This very loose space communicates with the vertebral-pharyngeal space and the deep pterygoid space of the masticator compartment. Floor of the mouth This is a very complex structure in which several intercommunicating compartments are subdivided by the many glossal and hyoid muscles. It is limited externally by the internal aspect of the mandibula, the platysma muscles with the superficial cervical aponeurosis and the skin. First division is in a superior and inferior compartment separated horizontally by the mylohyoid muscle. In the superior compartment there are two symmetrical lodges containing the sublingual glands and their respective Wartons duct, separated medially by the genioglossus, geniohyoid and hypoglossus muscles. The compartments also contain the lingual, hypoglossus nerves and vessels of the tongue. The inferior compartments are further divided in three: two lateral symmetrical submandibular fossae, containing the homonymous gland, lingual nerve, vessels and lymph nodes; and a median lodge, the sub-mental space, containing adipose tissue and lymph nodes, limited caudally by the cutaneous muscles of the neck.

Streptococci can also cause facial cellulitis.57,1416 In children, S. aureus and, to a lesser extent, Haemophilus influenzae are reported.1420 There are sporadic cases in both adults and children due to Streptococcus pneumoniae, Neisseria meningitidis, Klebsiella pneumoniae, Yersinia enterocolitis, Pseudomonas aeruginosa and Nocardia species.2127 A mixture of Gram-positive cocci and Gram-negative aerobes and anaerobes tends to be responsible for cellulitis after surgical procedures and dental pathologies. 46,28 Emergence of community methicillin-resistant Staphylococcus aureus (MRSA) has been seen across the world, 4,2937 although it is spreading at different rates. A 22% frequency of MRSA isolation associated with cellulitis has been reported. 30 Virulence and amounts of germs are important. Above all, however, predisposing local and general conditions are critical factors for the development of this severe infection. Compromised skin, such as underlying dermatoses or previous infection, especially due to Varicella zoster or trauma, and surgical wounds provide a portal of entry for bacterial pathogens.15,2127,3739 Body piercing has recently been reported as a possible cause of facial cellulitis.40

Regional anatomy explains the spread from very typical closed spaces, such as the oral cavity, orbit, upper respiratory tract, parotid gland and ear (see Table 2). Occurrence in the course of dental pathology28,38,39 is one of the most relevant causes, as different conditions whether gradual (caries, periodontal abscesses) or sudden (traumatic injury) can expose dental pulp to a varied population of bacteria covering mucous and dental surfaces or living inside the gingival sulci. Once the germs have reached the periapical space, spread and progression towards the bone (osteomyelitis) and/or the neighbouring soft tissue (cellulites) is a matter of time. Less frequently, bacteria are injected directly into the periodontal space in the course of surgical procedures, especially while performing oral anaesthesia. Deeper tissue contamination during surgery is the main source of infection after major procedures on the head and neck, especially after traumatic, vascular or neoplastic intervention.37 Infections can also spread from distant sites following the bloodstream and/or the lymphatics.16,39 Chronic and acute sinusitis, faringo-tonsillitis and otitis are frequently reported in patient histories,

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Cellulitis
Figure 1: A 41-year-old Man with Erythematous Ill-defined Swelling on the Central Face, Especially on the Left Jugal, Nasal and Inferior Eyelid Regions especially in children,1620 although usually cellulitis occurs in a moment of apparent wellness. The hosts defences are the other key factors in cellulitis development: functional deterioration of tissue is frequent in diabetes, kidney and liver insufficiency, malnutrition, vitamin deficiency and in the course of malignancies (especially in patients exposed to chemotherapy and radiation regimens).16 War is a condition in which facial cellulitis might rapidly develop from occult nasal infections or wounds.37 Immunodeficiency should always be suspected, primarily or as a consequence of systemic treatment, such as corticosteroids and cytostatics.35 MRSA should be suspected in patients with a history of previous general antibiotic regimens. MRSA is also steadily increasing among intravenous drug users, HIV-infected patients, prisoners, athletes, military trainees and male homosexuals.4143 Alcohol and other drug abuse are additional predisposing factors.
Permission for publication has been obtained from the patient.

Clinical Manifestations
Systemic symptoms, such as general malaise and fever with chills, usually precede the eruption and accompany the full development of the disease, which can take from hours to a few days.16 Cellulitis is characterised by an expanding area of erythema.1 All signs of inflammation are expressed: rubor, calor, dolor, tumour (see Figures 1 and 2). Borders are ill-defined in true cellulitis, with a typical dusky hue (see Figure 3). When involving the superior maxillary region, sudden presentation with a bluish halo has been indicated as bruised cheek syndrome to emphasise the similarity to an accidental traumatic injury; a mistake that can further delay the correct diagnosis.44 The surface usually breaks in some points with the appearance of vesicles and/or bullae (see Figure 3), as well as pustules that progress to necrotic tissue discharge (see Figure 4). Ascending lymphangitis might seldom be visible, but regional lymphadenopathy is usually constant, from mild to severe. The patient often suffers severe pain, with higher peripheral sensibility. Paraesthesia is frequently reported.16 The presence of hypo- or anaesthesia suggests deeper nerve involvement, which is characteristic of necrotising fasciitis, also known as flesh-eating bacteria syndrome.7,9 When involvement of the orbit is suspected, an accurate assessment reveals impaired painful ocular movements, ptosis and pro-ptosis of the eyelid, raised intraocular pressure and reduced or complete loss of trigeminal nerve sensation.45 In the oropharyngeal area, other alert signs suggestive of spread into cervical spaces are altered levels of consciousness, dehydratation, speech alteration, difficult breathing, dysphagia and intense lockjaw. A distinction of three stages has been proposed for acute cellulitis.28,46 The serous stage is the initial inflammatory process, which may resolve on its own or after appropriate treatment. It frequently develops into a suppurative phase, in which pus formation might be detected by palpation, producing the sign of fluctuation. If the abscess is deep, such as in the masticator compartment or the parapharyngeal space, imaging studies are necessary to reveal it. Once the pus is formed, resolution of the condition requires drainage spontaneously through a fistolisation phase or by means of a surgical procedure.

Figure 2: A 68-year-old Man with a More Severe and Diffuse Spreading Erythema of the Face, Progressing to Formation of Vesicles

Figure 3: Closer View of Eyelid Swelling with a Bluish Hue, Especially the Superior Eyelid and Vescicle Bullae of the Cheek

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Facial cellulitis can be further classified according to: localisation; severity; and evolution.

Figure 4: A 65-year-old Man with Severe Cellulitis of the Left Masseteric, Parotid, Submental, Submandibular and Homolateral Neck Compartment

Localisation
Anatomical disposition of the many facial muscles and aponeurotic compartments occupied by adipose cell tissue allows the delimitation of peculiar areas in which the infection is initially confined: parapharyngeal space, paratonsillar space, masticator compartment, sublingual and submandibular spaces, parotid space and superficial compartments comprising the Bichats fat pad covered by the maseter and buccinator muscles. Interconnections, especially through muscle insertion, allow the spread from distant sites of infection. For instance, infection of `the root of the upper molars spreads above the insertion of the buccinator, involving the genial region towards the lower eyelid, where the inflammatory oedema finally becomes apparent.28 The main resulting clinical features are maxillary or cheek cellulitis, neck and submandibolar cellulitis and infra-orbital orbital cellulitis.

The skin is diffusely red-purple, tender and not sharply demarcated, with a locally elevated temperature. Spontaneous sera-haematic confluent bullae rapidly progressed to ulcerations. A dense yellow necrotic material covers the fundus of the neck and supra-clavicularear ulcers. No crepitus was present at palpation.

Severity
Common forms are usually localised and tend to be less severe than very diffuse forms from the beginning. The best-known form of diffuse cellulitis is Ludwigs angina, characterised by the simultaneous involvement of the sublingual, submandibular, submental and eventually paratonsillar and parapharyngeal spaces. The imminent risk of asphyxia is an additional feature of this form.4751

because they are positive in a minority of cases and the isolates are usually the same as in the skin lesions.6,52,53 A swab culture of the nasopharynx is advisable to isolate the aetiological pathogen.37 Radiological examination is unnecessary in most cases of cellulitis, but facial involvement usually requires a panoramic X-ray plus lateral neck and/or ortopantomography to exclude subjacent osteomyelitis, dental pathologies, thickening of pre-vertebral soft tissue, displacement of the airways and eventual gas presence. 36 A computed tomography (CT) scan and magnetic resonance imaging (MRI) provide assessment of the extent of involvement and topographical limits. They detect abscesses and the presence of air within tissues.54 In a study involving 17 patients with suspected necrotising fasciitis,55 MRI identified all 11 cases of necrotising fasciitis (100% sensitivity), but misdiagnosed one of the six cases of cellulitis (86% specificity). The criteria for identifying necrotising fasciitis on MRI include the involvement of deep fasciae, as evidenced by fluid collection, thickening and enhancement with contrast material.4 Ultrasonography is of less value, but can help in detecting the subcutaneous accumulation of pus and in guiding aspiration.56 Biopsy is seldom performed because of the painful and difficult surgery, which would not grossly change the management of the condition. Histologically, the main features are deep dermal oedema, diffuse heavy neutrophil infiltration and vascular and lymphatic dilatation.57 Large numbers of bacteria are usually present and identifiable with special stains. Necrosis of epidermal keratinocytes and red cell extravasation are variable features, as is inflammatory perivascular infiltrate. In later stages, lymphocytes and histiocytes are also abundant, with granulation tissue formation, especially in deeper dermal areas. Occasional lymphocyte and neutrophil extension into the subcutaneous fat is possible, but should not be a prevalent feature. When clinical vescicolation is present, a corresponding severe papillary oedema is notable, merging with subepidermal bullae.58 The prevalence of necrosis and blood vessel involvement configuring necrotising vasculitis suggest a pathology of bacterial toxins.

Evolution
Cellulitis is mainly an acute process, but chronic and recurrent forms of cellulitis are also described.16 Chronic cellulitis is characterised by a painless oval or polycyclic nodule, covered by thin, violet-bluishcoloured skin. Common complications include necrotising fasciitis, thrombosis of the cavernous sinus, cerebral abscess, meningitis, mediastinitis and pneumonia, septicaemia and/or a toxic syndrome. Associated mortality is very high.21 Long-term complications include persistent lymphoedema, blindness and neurological sequelae. Correction of final skin loss might require plastic surgery.

Laboratory and Instrumental Findings and Histopathology

Complete blood count with differential usually demonstrates a slight leukocytosis with neutrophilia. However, it may be normal, especially in immunocompromised patients or when Gram-negative bacteria is involved.36,22,52 This condition is to be monitored, because a sudden decrease in blood count might precede shock in reaction to lipopolysaccharide release. A dose of blood C-reactive protein is important when the level is decreased, because ignored genetic or acquired deficiency has been related to a higher susceptibility to severe disease and progression towards necrotising fasciitis. Laboratory exudate cultures are not routinely performed,25 although identification of the pathogen and testing sensitivity to antibiotics are mandatory if the patient fails to respond to treatment within 48 hours. If the culture has not been performed in a timely manner, adjustment will be further delayed. Needle aspiration or a swab from lesions is the mainstay for diagnosis, while blood cultures are of limited use

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Differential Diagnoses
Cellulitis diagnosis is clinical, although cultural confirmation is always advisable. Concerning cephalic involvement, there are some benign and very common conditions that should be differentiated from cellulitis. Erysipelas is actually more frequent than frank cellulitis, but the two conditions require the same care and treatment, so differential diagnosis is a conclusive assessment.5,8 Herpes zoster is usually recognisable for its single dermatome disposition. Chronic sinusitis, periorbital inflammation and allergy (especially in young patients) can cause mild to moderate swelling of the cheek, nose and eyelid, which can be difficult to distinguish from the initial signs of cellulitis.59 Systemic upset and fever are usually absent in these benign conditions. Allergic manifestation, especially urticaria angioedema, as well as insect bites, tend to be itchy rather than painful. Carcinoma erysipeloides is sometimes confused with cellulitis at presentation, especially when metastasis involves the sphenoid and posterior wall of the orbit.60,61 Breast cancer is usually the primary tumour, followed by the prostate, lung, cervix and gastrointestinal tract.60 Absence of fever and a slower, more indolent course than cellulitis are distinctive features. Other conditions such as abscesses, necrotising fasciitis and gas gangrene are possible complications of cellulitis. They have to be ruled out in any case until recovery. Among inflammatory non-infective diseases, Sweets syndrome (acute febrile neutrophilic dermatosis) frequently mimics cellulitis on the face at presentation: acute, painful tender erythematous pseudovesiculated plaques, accompanied by fever, general malaise and neutrophilic leukocytosis.62,63 More generalised lesions can help in differentiating this entity from cellulitis. Pyoderma gangrenosum rarely occurs on the face, but acute lesions starting in the subcutaneous fat or superficial diffuse lesions might simulate cellulitis.6466 Wells eosinophilic cellulitis rarely involves the face, progresses slowly with erythematous oedematous lesions with central clearing and persists for weeks or months.67 All of these immunomediated entities are corticosteroid-sensitive, and broadspectrum antibiotics will not modify progression. the patients who develop cellulitis have major risk factors for MRSA infection, such as being very young children, having diabetes, immunosuppression, kidney and liver insufficiency, malnutrition, vitamin deficiency and alcohol and/or drug abuse.4,21,42,43 The main treatment options are penicillase-resistant penicillin (dicloxacillin, nafticillin, betalactam/clavulanic acid and piperacillin/tazobactam), often with an associated cephalosporin (cefazolin, ceftriaxone, cefalexin or cefadroxil). Penicillin-allergic patients can be given erythromycin or ciprofloxacin plus metronidazole. If symptoms do not improve after 2436 hours of treatment, intravenous antibiotics should be adjusted according to the results of culture and sensitivity tests. In very resistant infections, clindamycin or vancomycin is usually indicated, although susceptibility is decreasing.6871 New antibiotics with comparable efficacy to vancomycin are linezolid, quinupristindalfopristin and daptomycin.7278 Pain and fever control is initially indicated with oral analgesics and antipyretics, such as paracetamol, oxycodone and tramadol. The use of corticosteroids and/or non-steroidal anti-inflammatory drugs (NSAIDs) is controversial,79,80 as it may favour progression and mask the signs and symptoms of deeper necrotising infections. Local medication is a mainstay, with daily debridement and drainage of the purulent necrotic material followed by application of antibiotics. Wet dressing areas of bullae or exudates is recommended. Treatment of predisposing conditions is otherwise mandatory, such as blood sugar in patients with diabetes, chronic infections in children and dental pathologies in adults. Daily prophylaxis with oral penicillin should be considered for patients who have had more than two episodes of cellulitis at the same site.4

Conclusion
Cellulitis is an emergency that must be handled early. Facial involvement is particularly aggressive, as many anatomical sites naturally host bacteria and are potentially subject to concurrent diseases, accidental injuries and surgical procedures. Local and general predisposing conditions lead to induction of the disease. The submandibular region, cheek, eyes and orbit are among the most frequent locations of facial cellulitis. Any age can be affected, although infants and the elderly are at higher risk. Complications are fortunately rare but life-threatening, including thrombosis of the cavernous sinus, cerebral abscesses, meningitis, asphyxia, septicaemia, mediastinitis and pneumonia. Long-term complications include recurrences and persistent lymphoedema. Treatment for specific types of cellulitis may be tailored following microbiological findings based on cultures and drug sensitivities. Most patients recover completely after timely antibiotics. n

Treatment
Empirical use of broad-spectrum antibiotics is the first choice in cellulitis. Although the vast majority of soft-tissue infections are still due to Gram-positive organisms susceptible to beta-lactams and cephalosporins,57,14 MRSA and other penicillin-resistent bacteria2937 especially in mixed infections suggest wide, effective strategies. Delay in the use of the correct antibiotic may contribute to prolonged illness, hospitalisation and the occurence of complications. Moreover, many of

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1986;146:29597. Lewis R, Soft tissue infections, World J Surg, 1998;22:14651. Celestin R, Brown J, Kihiczak G, et al., Erysipelas: a common potentially dangerous infection, Acta Dermatovenerol Alp Panonica Adriat, 2007;16:1237. 9. File T, Ran J, Group A streptococcus necrotizing fasciitis, Com Ther, 2000;26:7381. 10. Crock GW, Wilson JH, Janakiraman P et al., Gas gangrene , infection of the eyes and orbits, Br J Ophthalmol, 1985;69:14348. 11. Brooke CJ, Riley TV, Erysipelotrix rhusiopathie: bacteriology, epidemiology and clinical manifestations of 7. 8.

an occupational pathogen, J Med Microbiol, 1999;48:78999. 12. Ellis Simonsen SM, van Orman ER, Hatch BE, et al., Cellulitis incidence in a defined population, Epidemiol Infect, 2006;134:2939. 13. Lipsky BA, Weigelt JA, Gupta V, et al., Skin, soft tissue, bone, and joint infections in hospitalized patients: epidemiology and microbiological, clinical, and economic outcomes, Infect Control Hosp Epidemiol, 2007;28:129098. 14. Chira S, Miller LG, Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review, Epidemiol Infect, 2010;138:31317. 15. Lamagni TL, Darenberg J, Luca-Harari B, et al.,

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