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Skin and soft tissue infections
SKIN AND SOFT TISSUE INFECTIONS
Skin and soft tissue infections
What’s new? C
ME Torok C
CP Conlon C
Increasing drug resistance in the two most common pathogens (S. aureus and group A streptococci) is a concern The incidence of severe infections such as necrotizing fasciitis appears to be increasing Community-acquired MRSA is emerging as an important cause of SSTI, particularly in the USA
Abstract Skin and soft tissue infections (SSTI) range from relatively common superficial skin infections to rare but life-threatening infections like necrotizing fasciitis or gas gangrene. They can affect all ages and predisposing factors include trauma, pre-existing dermatoses, diabetes, and immunocompromise. SSTI are often caused by organisms that colonize the skin, such as Staphylococcus aureus or group A streptococci, as a result of a breach in the skin’s integrity. Community-acquired meticillin-resistant S. aureus (CA-MRSA) is becoming increasingly important as a cause of SSTI. Less common causes include a variety of Gram-negative bacteria, fungi, viruses and parasites. Treatment is usually with topical or systemic antimicrobials, directed against the suspected organism, but urgent surgical debridement is sometimes required.
skin conditions, diabetes mellitus, alcoholism, malignancy or immune suppression). SSTIs may occur as single or recurrent episodes, and may be mild and self-limiting or severe and progressive, leading to necrosis of adjacent tissues. Clues to potentially severe deep soft-tissue infection include the following: pain disproportionate to the physical findings; violaceous bullae; cutaneous haemorrhage; skin sloughing; skin anaesthesia; rapid progression; gas in the tissue.1 A detailed history is essential to establish a specific diagnosis and should include the following: onset and duration of symptoms appearance and anatomical distribution of the lesion history of trauma or surgery contact with insects and other animals recent foreign travel pre-existing medical conditions previous antibiotic therapy. Patients who are systemically unwell should be admitted to hospital and have blood taken for full blood count, biochemical profile, inflammatory markers and blood cultures. When the diagnosis of an SSTI cannot be made on clinical grounds, investigations such as needle aspiration, punch biopsy or surgical debridement may be necessary. Empirical antimicrobial therapy should be directed towards the likely organism(s) and subsequently tailored in the light of microbiological data. Emerging antibiotic resistance among S. aureus (meticillin and erythromycin resistance) and group A streptococci (erythromycin resistance) is a concern. If meticillin-resistance is suspected, vancomycin should be part of the initial treatment regimen.
Keywords cellulitis; ecthyma; erysipelas; folliculitis; gas gangrene; group A streptococci, impetigo; necrotizing fasciitis; skin and soft tissue infection; Staphylococcus aureus
Introduction The skin acts as a barrier between the host and the environment. It comprises several layers. The most superficial is the epidermis, a thin avascular layer overlying the dermis, a thicker layer containing hair follicles, sebaceous glands and sweat glands. Subcutaneous fat lies beneath the dermis and is separated from muscle by a tough layer of fascia (see the article by JE LaiCheong and JA McGrath, Medicine, 2009; 37: 223e226 for more information). Infections may affect one or more of these layers. The skin is colonized by micro-organisms that have the potential to invade and cause infection. Staphylococcus aureus and Group A streptococci are the most important pathogens,1 but other organisms such as Gram-negative bacteria, anaerobic bacteria, viruses, fungi, or parasites can also cause infection. Community-acquired meticillin-resistant S. aureus (CA-MRSA) has become an important cause of skin and soft tissue infections (SSTI), particularly in the USA.2,3 SSTIs are common and can affect all age groups. Certain conditions may predispose to SSTIs (e.g. trauma, pre-existing
Impetigo Impetigo is a superficial pyogenic infection of the epidermis, usually caused by S. aureus or Group A streptococci. It usually affects young children and is more common in hot, humid climates. It can cause outbreaks in households, institutions and sports teams. Patients often report a history of minor skin trauma, insect bites or pre-existing dermatoses. Lesions typically occur on the face and hands. Impetigo is characterized by intraepidermal vesicles, which rupture and crust to form a goldenyellow scab. Constitutional symptoms are usually absent. Impetigo is treated by removal of the crusts and application of topical antibiotics such as mupirocin. Widespread infection responds better to oral or intravenous antibiotics (e.g. flucloxacillin or clindamycin).
ME Torok MA MRCP FRCPath is a Consultant in Infectious Diseases in the Department of Infectious Diseases, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared. CP Conlon MA MD FRCP is a Consultant in Infectious Diseases, in the Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK. Competing interests: none declared.
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Ecthyma
may need to cover MRSA if the patient is colonized). Pseudomonas folliculitis is usually self-limiting but oral ciprofloxacin may be given if lesions are persistent or the patient is immunocompromised. Pityrosporum folliculitis usually responds to topical antifungals (e.g. ketoconazole cream). Herpetic folliculitis responds to oral antivirals (e.g. valaciclovir). Eosinophilic folliculitis may respond to isotretinoin, metronidazole, UV-B phototherapy, indometacin or itraconazole. Folliculitis associated with EGF-R inhibitors is usually self-limiting.
Ecthyma is a form of impetigo that penetrates deeper into the dermis and may scar. It starts as a vesicle and progresses to form a punched-out ulcer surrounded by a violaceous border (Figure 1). Ecthyma often occurs on the legs and is associated with minor trauma, insect bites, eczema, pediculosis, diabetes, and immunodeficiency. Most cases are caused by group A streptococci. A similar lesion called ‘ecthyma gangrenosum’ is usually associated with Pseudomonas aeruginosa bacteraemia,4 but has been reported with other organisms (e.g. MRSA, Citrobacter freundii, and Stenotrophomonas maltophilia). Ecthyma may be treated with topical mupirocin for mild cases and oral penicillin or clindamycin for more severe cases. Ecthyma gangrenosum should be treated with appropriate antibiotics, depending on the causative organism.
Furuncles and carbuncles Folliculitis may progress to involve the dermis, resulting in the development of a subcutaneous boil or abscess (furuncle). The usual cause is S. aureus. A number of furuncles may coalesce, resulting in the formation of a ‘carbuncle’ (Figure 2). Carbuncles are characterized by inflamed skin with pus draining from several hair follicles. Carbuncles are commonly found on areas of thickened skin such as the nape of the neck, the back and the thighs. Fever and malaise are common. Rarely, recurrent furuncles become a problem. Diabetes mellitus, and rare causes of immunodeficiency, such as hyper-IgE syndrome (Job’s syndrome) and chronic granulomatous disease, should be considered. Small furuncles may burst and heal spontaneously; larger ones may require incision and drainage. Carbuncles usually require incision and drainage along with systemic antimicrobials (e.g. oral or intravenous flucloxacillin). Patients with recurrent furuncles who do not have underlying immunodeficiency should be considered for staphylococcal decolonization using mupirocin 2% nasal ointment and chlorhexidine gluconate 4% shampoo/ body wash.
Folliculitis Folliculitis is an inflammation of the hair follicles that is characterized by clusters of small, erythematous papules or pustules. Any hair-bearing site can be affected, but the sites most often involved are the face, scalp, thighs, axilla, and inguinal area. Certain conditions make patients more susceptible (e.g. frequent shaving, pre-existing skin conditions, occlusive clothing/dressings, exposure to hot humid temperatures, diabetes mellitus, obesity, long-term antibiotic or corticosteroid use, and immunosuppression). The most common form of folliculitis is sycosis barbae (barber’s itch), which is caused by S. aureus. Tinea barbae is a fungal folliculitis, caused by various dermatophytes, that resembles its bacterial counterpart. Other infectious causes include Enterobacteriaceae (often associated with prolonged antibiotic therapy). P. aeruginosa (associated with hot tubs and wet suits),5 Pityrosporum orbiculare (Malassezia furfur), herpes simplex virus, varicella-zoster virus and Demodex mites. Non-infectious causes include eosinophilic folliculitis (thought to be an autoimmune process directed against the sebocytes)6 and a papulopustular follicular eruption that occurs after treatment with epidermal growth factor receptor (EGF-R) inhibitors.7 For recurrent uncomplicated superficial folliculitis, antibacterial soaps and good hygiene may be all that is required. For refractory or deep infections systemic antibiotics may be required (e.g. oral flucloxacillin for staphylococcal folliculitis; treatment
Erysipelas Erysipelas is a superficial bacterial infection of the dermis that also involves the cutaneous lymphatics. It is characterized by
Figure 1 Ecthyma in an immunocompromised patient.
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Figure 2 Carbuncle on the dorsum of the foot.
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abrupt onset of a painful, erythematous, spreading rash with well-demarcated edges (Figure 3). There are often systemic features (e.g. fever, malaise, chills), which may precede the onset of skin lesions, and bacteraemia occurs in <5% of patients. Historically, erysipelas typically affected the face and was caused by group A streptococci.8 However, a shift in the distribution and aetiology of the disease has occurred, with most erysipelas infections now occurring on the lower extremities, and with non-group A streptococci being increasingly identified as the causative agents. Recently, atypical forms, caused by Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Yersinia enterocolitica, and Moraxella spp., have been described. Predisposing factors include skin conditions (e.g. eczema, ulcers, dermatophyte infections), venous stasis, paraparesis, diabetes, nephrotic syndrome, alcohol abuse and immunodeficiency). Erysipelas tends to occur in areas of lymphatic obstruction and, because it also causes lymphatic obstruction, tends to recur. Treatment is with intravenous benzylpenicillin. In penicillinallergic patients clindamycin may be used instead. Anti-staphylococcal therapy (flucloxacillin or vancomycin) is not usually considered necessary unless patients fail to improve with penicillin or have features suggestive of staphylococcal infection (e.g. bullous erysipelas).
Figure 4 Cellulitis of the lower limb.
Cellulitis area that is not as well demarcated or elevated as in erysipelas. Thrombophlebitis, lymphangitis, regional lymphadenopathy and fever are common. Local abscesses may develop and the overlying skin can become necrotic. The diagnosis of cellulitis is almost entirely clinical; skin swabs are unhelpful and blood cultures, skin biopsies and tissue aspirates are seldom positive. Patients with mild cellulitis and no systemic symptoms can be treated with oral or intravenous flucloxacillin; clindamycin is an alternative in penicillin-allergic patients. If the patient is diabetic or has leg ulcers, Gram-negative organisms and anaerobes are more likely, so intravenous co-amoxiclav may be used instead. Intravenous vancomycin should be used for cellulitis in patients who are known to be MRSA colonized. Teicoplanin or linezolid are suitable alternatives. Analgesia, elevation of the limb and subcutaneous heparin are useful adjunctive measures. A surgical opinion should be sought if there is circumferential cellulitis or necrotic skin.
Cellulitis is rapidly spreading inflammation of the deep dermis and subcutaneous fat (Figure 4). The most common pathogens are S. aureus and group A streptococci.9 Cellulitis caused by CA-MRSA is becoming increasingly common2 and has been reported in sports teams.10,11 Rarer causes include groups B, C and G streptococci, S. pneumoniae, Enterobacteriaceae, Pseudomonas spp., Pasteurella multocida (associated with animal contact), Aeromonas hydrophila and Vibrio vulnificus (associated with freshwater and salt water contact respectively). Cellulitis generally occurs after injury to the skin or as a result of breaches of the skin (e.g. ulcers, eczema, psoriasis, tinea infections). Patients with diabetes, leg ulcers, lymphoedema, varicose veins or peripheral vascular disease are at increased risk. Cellulitis usually affects the legs and presents as a red, hot, swollen, tender
Bursitis Bursitis is an inflammation of a bursa which may be caused by repetitive use, trauma, gout, rheumatoid arthritis, or infection (septic bursitis). Septic bursitis occurs from direct inoculation of micro-organisms through the skin or spread from adjacent cellulitis; rarely it may occur as a result of haematogenous spread. S. aureus is the predominant cause followed by streptococci and, rarely, mycobacteria or fungi. Predisposing factors include trauma, skin diseases, diabetes, alcoholism, and corticosteroid therapy. The diagnosis is clinical and based on fever plus swelling, erythema and tenderness over the affected bursa. The most common sites are the olecranon and pre-patellar bursa. Treatment is with intravenous flucloxacillin, elevation of the limb and, if necessary, aspiration of pus from the affected bursa.
Figure 3 Erysipelas caused by group A streptococcus.
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type of animal and status (behaviour, health, rabies vaccination) circumstances surrounding the bite (e.g. provoked or unprovoked) location of bite (most often on face or upper extremities) pre-hospital treatment patient’s medical history (e.g. diabetes, immunocompromised, tetanus and rabies vaccination status). Wounds on the extremities should be assessed carefully for evidence of damage to joints, muscles, tendons, nerves and blood vessels. Specialist surgeons should be consulted for wounds involving the face or hands. Prophylactic co-amoxiclav has been shown to be effective. Treatment involves copious wound irrigation, debridement, elevation of the affected part and, if appropriate, tetanus and rabies immunization. Primary wound closure is usually undertaken only for facial wounds. Magnetic resonance imaging (MRI) should be performed if there is clinical suspicion of osteomyelitis. Human bites should be managed with prophylactic antibiotics, but the risk of blood-borne viral infections should be considered. Recipients of monkey bites should be given prophylactic valaciclovir or aciclovir because of the risk of simian herpes virus B.
In penicillin-allergic or MRSA-colonized patients, vancomycin is appropriate. Surgical drainage is rarely required.
Surgical-site infections Although the prevalence of surgical site infections (SSIs) has reduced with the use of antibiotic prophylaxis, they continue to be an important cause of hospital-acquired infection. Several factors are known to contribute to the risk of SSI: host (age, nutritional status, immune status, perioperative conditions, e.g. blood glucose, body temperature and oxygenation) surgical (type of procedure, surgical technique, use of foreign material) microbial (concentration and virulence of organisms, resistance to antimicrobial prophylaxis). SSIs can be divided into three types: superficial incisional (involving skin or subcutaneous tissues); deep incisional (involving fascia or muscle); and organ/space infection. The infecting organisms are usually the patient’s endogenous flora. S. aureus (including MRSA), coagulase-negative staphylocci and enterococci are the most common organisms. However, depending of the site of surgery (e.g. gastrointestinal), Enterobacteriaceae, anaerobes and Candida spp. may be implicated. Most superficial incisional SSIs present within days after the operation, with fever and local pain, swelling, erythema, tenderness, a purulent discharge or wound dehiscence. Ultrasonography or computed tomography (CT) may be required to identify deep incisional SSI in patients with clinical evidence of systemic infection but no local signs. Management of surgical wound infection primarily involves incision and drainage, debridement of any necrotic tissue, removal of any foreign material, and local wound care. A deep pus or tissue sample should be sent for microbiological examination. Surface swabs are not useful because they merely reflect colonizing organisms. Most superficial wound infections do not require any further therapy. The need for antimicrobial therapy should be guided by clinical findings (e.g. spreading cellulitis, systemic symptoms). The initial choice of antimicrobial agent should be directed towards the most likely organisms, according to the type of operation performed. Treatment can then be tailored in light of microbiological findings. Most incisional surgical wound infections are left open and allowed to heal by secondary intention.
Infections in intravenous drug-users Intravenous drug-users often introduce bacteria into normally sterile sites. Although septicaemia and endocarditis are the greatest dangers, skin and soft tissue infections are more common (Figure 5).13 The most common organism is S. aureus, but oral flora (e.g. a-haemolytic streptococci, Neisseria spp., Haemophilus spp. and Eikenella corrodens) may be found in those who lick their needles. Other causes include S. pneumoniae, Gram-negative bacteria, Clostridia spp. and fungi. In 2000 a high fatality outbreak of SSTI occurred in the UK due to heroin contaminated with Clostridium novyi.14 Cellulitis or abscesses might occur at the site of injection and can cause considerable soft tissue damage. Injections might also
Bite infections Bite wounds are usually caused by domestic pets, e.g. dogs (most common), cats, rabbits, guinea pigs, reptiles and occasionally monkeys. It is estimated that 3e18% of dog wounds and 28e 80% of cat wounds become infected. Although most attention has focused on Pasteurella multocida, a wide spectrum of organisms has been isolated from bite wounds (e.g. staphylococci, streptococci, enterococci, Neisseria spp., Haemophilus spp., Eikenella spp., Enterobacteriaceae, Capnocytophaga canimorsus, and anaerobes).12 Human bite infections are usually associated with oral flora. Assessment for animal bite infections should include the following:
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Figure 5 Injection abscess in an intravenous drug-user.
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cause intramuscular abscesses (pyomyositis) or necrotizing fasciitis. Complications include bacteraemia, septic arthritis, osteomyelitis and infectious endocarditis. Treatment is with intravenous antibiotics and, usually, surgical drainage or debridement.
assessing the need for further surgery. Adjunctive therapies such as intravenous immunoglobulin and hyperbaric oxygen have been advocated.
Necrotizing fasciitis
Fournier’s gangrene is a form of necrotizing fasciitis that affects the genital, perineal and perianal regions. Most cases occur in patients aged 30e60 years and there is a 10:1 male to female ratio. Risk factors include advanced age, diabetes, alcohol abuse, colorectal disease/surgery, malignancy, malnutrition and immunosuppression. Men who have sex with men may be at higher risk, especially for infections caused by CA-MRSA. Fournier’s gangrene is a polymicrobial infection caused by a mixture of aerobic (e.g. Enterobacteriaceae, streptococci, enterococci, Pseudomonas spp.), and anaerobic (e.g. Bacteroides spp., Clostridium spp.) bacteria. The incidence of MRSA infections appears to be increasing. Symptoms usually begin with the insidious onset of pruritus and discomfort in the external genitalia. This is followed by swelling and erythema of the genital/perineal region and associated with severe pain and systemic symptoms. Fournier’s gangrene, like necrotizing fasciitis in other settings, is a surgical emergency that requires prompt surgical debridement and broad-spectrum intravenous antibiotic therapy (e.g. coamoxiclav, metronidazole and gentamicin). Vancomycin should be given if the patient is known or likely to be MRSA colonized. Consider a tetanus booster if immunization status is unknown e there have been cases of fatal tetanus associated with Fournier’s gangrene.
Fournier’s gangrene
Necrotizing fasciitis is an uncommon severe infection that results in destruction of subcutaneous tissue and fascia (Figure 6). Predisposing factors include diabetes, alcoholism and intravenous drug use. There are two clinical types: Type I necrotizing fasciitis is a mixed infection caused by streptococci, Enterobacteriaceae, Bacteroides spp., and Peptostreptococcus spp. It occurs in middle-aged and elderly individuals, most commonly after surgical procedures, and in those with diabetes or peripheral vascular disease. Infection usually starts in the feet and progresses rapidly along the fascia into the leg. Clinical presentation is with cellulitis and systemic signs of severe infection. Type I necrotizing fasciitis may also develop in the head and neck following a breach of the mucous membranes by surgery or instrumentation. Type II necrotizing fasciitis is caused by group A streptococci8 and was previously termed ‘streptococcal gangrene’. It may occur in any age group. The cardinal symptom is excruciating pain with minimal cutaneous findings. Initially, there may also be fever, malaise, myalgia and diarrhoea. After 24e48 h, erythema may develop, the skin may darken to a reddish-purple colour and bullae may develop. Patients are systemically unwell and may develop streptococcal toxic shock syndrome. CA-MRSA is increasingly recognized as a cause of necrotizing fasciitis in the USA.15 MRI might show subcutaneous and fascial oedema in addition to gas in the tissues. However, imaging must not delay prompt surgical exploration in patients in whom the diagnosis is clearly suspected. Necrotizing fasciitis is a surgical emergency and requires prompt surgical debridement. Intravenous broad-spectrum antibiotics (e.g. co-amoxiclav, clindamycin and gentamicin) are given until microbiological data are available. Clindamycin has a theoretical advantage in that it may interrupt toxin production and reduce systemic toxic effects. Patients often require intensive care. Imaging studies may be helpful for monitoring progress and
Gas gangrene Gas gangrene and clostridial myonecrosis are terms used to describe a rare infection caused by toxin-producing clostridia. Clostridium perfringens is the predominant cause, although other clostridial and non-clostridial species have been implicated. It is usually associated with contamination of traumatic or surgical wounds with clostridia, which then multiply in anaerobic conditions and produce exotoxins that result in tissue damage. Clinical features include the sudden onset of pain 6e8 h after injury. This is followed by increasing pain and tenderness, darkening of the skin to a purplish-red colour, formation of bullae, crepitus, fever, shock, haemolytic anaemia, liver and renal failure. Gas in the soft tissues may be confirmed by plain radiography, CT or MRI. The diagnosis is confirmed by demonstration of Gram-positive rods in the affected tissue. Management is with aggressive surgical debridement combined with intravenous antibiotics (e.g. penicillin and clindamycin). Intensive care support and multiple debridements may be required. The use of adjuvant therapies (e.g. recombinant human activated protein C, hyperbaric oxygen) is controversial.
Uncommon infections Bacterial Anthrax is caused by Bacillus anthracis and most commonly affects the skin, resulting in a ‘malignant pustule’. Infections occur in abattoir workers and result from inoculation of
Figure 6 Necrotizing fasciitis affecting the buttock.
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Parasitic Cutaneous larva migrans occurs in returning travellers, particularly those who have visited tropical beaches. It is caused by infection with animal hookworm larvae such as Ancylostoma brasiliense, Ancylostoma caninum and Uncinaria stenocephala, and presents as an itchy cluster of lesions or a sinuous track on exposed areas. Treatment is with albendazole. Leishmaniasis e cutaneous leishmaniasis is acquired from a sandfly bite. ‘Old world’ leishmaniasis, caused by Leishmania major, Leishmania tropica and Leishmania aethiopica, is endemic in Africa, Asia, India, the Middle East and the Mediterranean. ‘New world’ leishmaniasis, caused by Leishmania brasiliensis, Leishmania mexicana and Leishmania panamensis, is endemic in Latin America. Clinical presentation is with a crusted sore on the face, hand or leg 6e8 weeks after returning from an endemic area. Diagnosis is clinical and confirmed histologically. Lesions often resolve spontaneously, but some may require cryotherapy or treatment with pentavalent antimony, amphotericin or pentamidine. Patients with L. brasiliensis should be treated to avoid the possibility of espundia (mucocutaneous disease).
bacterial spores into skin abrasions caused by handling the hides of infected animals. After a few days, a papule forms at the site of infection; this develops into a vesicle and ulcerates to form a necrotic centre or eschar. Local oedema, painful regional lymphadenopathy and systemic features are often present. The diagnosis is confirmed by demonstrating Gram-positive bacilli in the ulcer fluid or tissues and by culturing the organism. Penicillin therapy is adequate, though quinolones and tetracyclines are also effective. An anthrax vaccine is available for military use. Cat-scratch disease e Bartonella henselae is the most common cause. Clinical features include regional lymphadenopathy, fever and a red papule at the inoculation site. Atypical presentations include Parinaud’s ocular glandular syndrome, maculopapular rash, erythema multiforme, erythema nodosum and leucocytoclastic vasculitis. The diagnosis is confirmed serologically and by polymerase chain reaction analysis. Treatment is with azithromycin or doxycycline. Erysipeloid is a rare condition is caused by Erysipelothrix rhusiopathiae. It is usually acquired from infected animals, and affects veterinary surgeons, farmers and butchers. The organism is inoculated into the skin and causes characteristic dark, purplish lesions with swelling of the digits. Rarely, septicaemia occurs and may be complicated by endocarditis. The condition is treated with penicillin. Erythema chronicum migrans is the cutaneous manifestation of Lyme disease, which is caused by Borrelia burgdorferi. It is acquired by inoculation from a tick bite. A red, circular lesion develops and spreads from the site of the bite. Other features include fever, malaise and arthralgia. Diagnosis is serological. Treatment is with doxycycline. Tick typhus e African tick typhus, caused by Rickettsia conorii and Rickettsia africae is commonly seen in patients returning from safari in southern Africa. Endemic typhus is caused by Rickettsia typhi and transmitted by the rat flea. Epidemic typhus is caused by Rickettsia prowazekii and transmitted by the human louse. Clinical features include fever, headache, malaise, myalgia, lymphadenopathy and splenomegaly. There may be an eschar at the site of inoculation and a maculopapular rash, though some spotted fevers produce few if any spots. Diagnosis is confirmed serologically. Treatment is with doxycycline.
Viral Herpes zoster or shingles is caused by reactivation of varicella-zoster virus infection and is characterized by a painful, vesicular eruption in a dermatomal distribution. Risk factors include increasing age, immunosuppression (e.g. transplantation, HIV infection, corticosteroid therapy) and autoimmune disease. Complications include post-herpetic neuralgia, secondary bacterial skin infection, herpes zoster opthalmicus, Ramsay Hunt syndrome (herpes zoster oticus), aseptic meningitis. Treatment is with oral valaciclovir (for uncomplicated zoster) or intravenous acyclovir for immunocompromised patients or those with ocular involvement. Herpetic whitlow (herpes simplex infection of the skin) occurs as a complication of oral or genital herpes simplex virus infection. It is characterized by a painful, erythematous vesicular or pustular skin lesion. There may be associated fever and lymphadenopathy. The diagnosis is based on exposure history. Herpetic whitlow usually resolves spontaneously in 2e3 weeks but some recommend treatment with oral acyclovir. Molluscum contagiosum is a benign condition caused by a pox virus. It usually affects children or the immunocompromised (e.g. HIV-infected patients). The lesions are most commonly seen on the face and trunk, and are papular with a central punctum. Orf is an infectious cutaneous lesion caused by a pox virus acquired from sheep. It commonly affects farmers (particularly those who bottle-feed lambs) and veterinary surgeons. A red papule develops, commonly on the sides of the fingers, and grows rapidly, often becoming vesicular, before developing a central necrotic area. Lymphangitis, regional lymphadenopathy and fever are common. Recovery is spontaneous.
Mycobacterial Leprosy e infection with Mycobacterium leprae causes a spectrum of clinical disease ranging from tuberculoid to lepromatous leprosy. In tuberculoid leprosy, anaesthetic macules or plaques, pigmentary change and thickened peripheral nerves develop. In lepromatous leprosy, macules, papules, nodules and ulceration occur, resulting in collapse of the nasal bones and coarsening of facial tissues, producing the characteristic ‘leonine’ facies. The diagnosis is confirmed by biopsy and split-skin smears. Treatment is with dapsone, clofazimine and rifampicin. Lupus vulgaris is a cutaneous infection caused by M. tuberculosis. It most commonly affects the face and neck, and appears as firm, translucent, yellow-brown ‘apple jelly’ nodules. Untreated lesions spread, leading to disfiguring scarring and contractures. Diagnosis is confirmed by biopsy, which shows tuberculoid granulomata in the mid-dermis. Treatment is with antituberculous chemotherapy.
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Ectoparasites Scabies is a pruritic skin lesion caused by infestation with Sarcoptes scabei. It is associated with poor socioeconomic conditions and overcrowding. The female mite lays her eggs in
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10 Begier EM, Frenette K, Barrett NL, et al. A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 2004; 39: 1446e53. 11 Kazakova SV, Hageman JC, Matava M, et al. A clone of methicillinresistant Staphylococcus aureus among professional football players. N Engl J Med 2005; 352: 468e75. 12 Brook I. Microbiology and management of human and animal bite wound infections. Prim Care 2003; 30: 25e39. v. 13 Ebright JR, Pieper B. Skin and soft tissue infections in injection drug users. Infect Dis Clin North Am 2002; 16: 697e712. 14 Jones JA, Salmon JE, Djuretic T, et al. An outbreak of serious illness and death among injecting drug users in England during 2000. J Med Microbiol 2002; 51: 978e84. 15 Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 2005; 352: 1445e53.
a burrow in the stratum corneum, generating a local hypersensitivity reaction; when the eggs hatch, the cycle is repeated. Diagnosis is confirmed by extraction of the mite from a burrow. Treatment comprises topical acaricides (e.g. permethrin) and washing of all clothing and linen. All members of the household should be treated at the same time. So-called Norwegian scabies is a severe form with extensive crusting, most commonly seen in HIV infection. A
REFERENCES 1 Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005; 41: 1373e406. 2 King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and softtissue infections. Ann Intern Med 2006; 144: 309e17. 3 Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666e74. 4 Greene SL, Su WP, Muller SA. Pseudomonas aeruginosa infections of the skin. Am Fam Physician 1984; 29: 193e200. 5 Gregory DW, Schaffner W. Pseudomonas infections associated with hot tubs and other environments. Infect Dis Clin North Am 1987; 1: 635e48. 6 Nervi SJ, Schwartz RA, Dmochowski M. Eosinophilic pustular folliculitis: a 40 year retrospect. J Am Acad Dermatol 2006; 55: 285e9. 7 Duvic M. EGFR inhibitor-associated acneiform folliculitis: assessment and management. Am J Clin Dermatol 2008; 9: 285e94. 8 Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334: 240e5. 9 Swartz MN. Clinical practice. Cellulitis. N Engl J Med 2004; 350: 904e12.
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Skin and soft tissue infections remain a common clinical problem The diagnosis is predominantly based on clinical features Patients with systemic features should be admitted for evaluation Empirical therapy should be targeted against the most likely infecting organism(s) and targeted in the light of microbiological data Urgent surgical debridement may be required for certain infections
Ó 2009 Elsevier Ltd. All rights reserved.
Skin and soft tissue infections
What’s new? C
ME Torok C
CP Conlon C
Increasing drug resistance in the two most common pathogens (S. aureus and group A streptococci) is a concern The incidence of severe infections such as necrotizing fasciitis appears to be increasing Community-acquired MRSA is emerging as an important cause of SSTI, particularly in the USA
Abstract Skin and soft tissue infections (SSTI) range from relatively common superficial skin infections to rare but life-threatening infections like necrotizing fasciitis or gas gangrene. They can affect all ages and predisposing factors include trauma, pre-existing dermatoses, diabetes, and immunocompromise. SSTI are often caused by organisms that colonize the skin, such as Staphylococcus aureus or group A streptococci, as a result of a breach in the skin’s integrity. Community-acquired meticillin-resistant S. aureus (CA-MRSA) is becoming increasingly important as a cause of SSTI. Less common causes include a variety of Gram-negative bacteria, fungi, viruses and parasites. Treatment is usually with topical or systemic antimicrobials, directed against the suspected organism, but urgent surgical debridement is sometimes required.
skin conditions, diabetes mellitus, alcoholism, malignancy or immune suppression). SSTIs may occur as single or recurrent episodes, and may be mild and self-limiting or severe and progressive, leading to necrosis of adjacent tissues. Clues to potentially severe deep soft-tissue infection include the following: pain disproportionate to the physical findings; violaceous bullae; cutaneous haemorrhage; skin sloughing; skin anaesthesia; rapid progression; gas in the tissue.1 A detailed history is essential to establish a specific diagnosis and should include the following: onset and duration of symptoms appearance and anatomical distribution of the lesion history of trauma or surgery contact with insects and other animals recent foreign travel pre-existing medical conditions previous antibiotic therapy. Patients who are systemically unwell should be admitted to hospital and have blood taken for full blood count, biochemical profile, inflammatory markers and blood cultures. When the diagnosis of an SSTI cannot be made on clinical grounds, investigations such as needle aspiration, punch biopsy or surgical debridement may be necessary. Empirical antimicrobial therapy should be directed towards the likely organism(s) and subsequently tailored in the light of microbiological data. Emerging antibiotic resistance among S. aureus (meticillin and erythromycin resistance) and group A streptococci (erythromycin resistance) is a concern. If meticillin-resistance is suspected, vancomycin should be part of the initial treatment regimen.
Keywords cellulitis; ecthyma; erysipelas; folliculitis; gas gangrene; group A streptococci, impetigo; necrotizing fasciitis; skin and soft tissue infection; Staphylococcus aureus
Introduction The skin acts as a barrier between the host and the environment. It comprises several layers. The most superficial is the epidermis, a thin avascular layer overlying the dermis, a thicker layer containing hair follicles, sebaceous glands and sweat glands. Subcutaneous fat lies beneath the dermis and is separated from muscle by a tough layer of fascia (see the article by JE LaiCheong and JA McGrath, Medicine, 2009; 37: 223e226 for more information). Infections may affect one or more of these layers. The skin is colonized by micro-organisms that have the potential to invade and cause infection. Staphylococcus aureus and Group A streptococci are the most important pathogens,1 but other organisms such as Gram-negative bacteria, anaerobic bacteria, viruses, fungi, or parasites can also cause infection. Community-acquired meticillin-resistant S. aureus (CA-MRSA) has become an important cause of skin and soft tissue infections (SSTI), particularly in the USA.2,3 SSTIs are common and can affect all age groups. Certain conditions may predispose to SSTIs (e.g. trauma, pre-existing
Impetigo Impetigo is a superficial pyogenic infection of the epidermis, usually caused by S. aureus or Group A streptococci. It usually affects young children and is more common in hot, humid climates. It can cause outbreaks in households, institutions and sports teams. Patients often report a history of minor skin trauma, insect bites or pre-existing dermatoses. Lesions typically occur on the face and hands. Impetigo is characterized by intraepidermal vesicles, which rupture and crust to form a goldenyellow scab. Constitutional symptoms are usually absent. Impetigo is treated by removal of the crusts and application of topical antibiotics such as mupirocin. Widespread infection responds better to oral or intravenous antibiotics (e.g. flucloxacillin or clindamycin).
ME Torok MA MRCP FRCPath is a Consultant in Infectious Diseases in the Department of Infectious Diseases, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared. CP Conlon MA MD FRCP is a Consultant in Infectious Diseases, in the Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK. Competing interests: none declared.
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Ecthyma
may need to cover MRSA if the patient is colonized). Pseudomonas folliculitis is usually self-limiting but oral ciprofloxacin may be given if lesions are persistent or the patient is immunocompromised. Pityrosporum folliculitis usually responds to topical antifungals (e.g. ketoconazole cream). Herpetic folliculitis responds to oral antivirals (e.g. valaciclovir). Eosinophilic folliculitis may respond to isotretinoin, metronidazole, UV-B phototherapy, indometacin or itraconazole. Folliculitis associated with EGF-R inhibitors is usually self-limiting.
Ecthyma is a form of impetigo that penetrates deeper into the dermis and may scar. It starts as a vesicle and progresses to form a punched-out ulcer surrounded by a violaceous border (Figure 1). Ecthyma often occurs on the legs and is associated with minor trauma, insect bites, eczema, pediculosis, diabetes, and immunodeficiency. Most cases are caused by group A streptococci. A similar lesion called ‘ecthyma gangrenosum’ is usually associated with Pseudomonas aeruginosa bacteraemia,4 but has been reported with other organisms (e.g. MRSA, Citrobacter freundii, and Stenotrophomonas maltophilia). Ecthyma may be treated with topical mupirocin for mild cases and oral penicillin or clindamycin for more severe cases. Ecthyma gangrenosum should be treated with appropriate antibiotics, depending on the causative organism.
Furuncles and carbuncles Folliculitis may progress to involve the dermis, resulting in the development of a subcutaneous boil or abscess (furuncle). The usual cause is S. aureus. A number of furuncles may coalesce, resulting in the formation of a ‘carbuncle’ (Figure 2). Carbuncles are characterized by inflamed skin with pus draining from several hair follicles. Carbuncles are commonly found on areas of thickened skin such as the nape of the neck, the back and the thighs. Fever and malaise are common. Rarely, recurrent furuncles become a problem. Diabetes mellitus, and rare causes of immunodeficiency, such as hyper-IgE syndrome (Job’s syndrome) and chronic granulomatous disease, should be considered. Small furuncles may burst and heal spontaneously; larger ones may require incision and drainage. Carbuncles usually require incision and drainage along with systemic antimicrobials (e.g. oral or intravenous flucloxacillin). Patients with recurrent furuncles who do not have underlying immunodeficiency should be considered for staphylococcal decolonization using mupirocin 2% nasal ointment and chlorhexidine gluconate 4% shampoo/ body wash.
Folliculitis Folliculitis is an inflammation of the hair follicles that is characterized by clusters of small, erythematous papules or pustules. Any hair-bearing site can be affected, but the sites most often involved are the face, scalp, thighs, axilla, and inguinal area. Certain conditions make patients more susceptible (e.g. frequent shaving, pre-existing skin conditions, occlusive clothing/dressings, exposure to hot humid temperatures, diabetes mellitus, obesity, long-term antibiotic or corticosteroid use, and immunosuppression). The most common form of folliculitis is sycosis barbae (barber’s itch), which is caused by S. aureus. Tinea barbae is a fungal folliculitis, caused by various dermatophytes, that resembles its bacterial counterpart. Other infectious causes include Enterobacteriaceae (often associated with prolonged antibiotic therapy). P. aeruginosa (associated with hot tubs and wet suits),5 Pityrosporum orbiculare (Malassezia furfur), herpes simplex virus, varicella-zoster virus and Demodex mites. Non-infectious causes include eosinophilic folliculitis (thought to be an autoimmune process directed against the sebocytes)6 and a papulopustular follicular eruption that occurs after treatment with epidermal growth factor receptor (EGF-R) inhibitors.7 For recurrent uncomplicated superficial folliculitis, antibacterial soaps and good hygiene may be all that is required. For refractory or deep infections systemic antibiotics may be required (e.g. oral flucloxacillin for staphylococcal folliculitis; treatment
Erysipelas Erysipelas is a superficial bacterial infection of the dermis that also involves the cutaneous lymphatics. It is characterized by
Figure 1 Ecthyma in an immunocompromised patient.
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Figure 2 Carbuncle on the dorsum of the foot.
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abrupt onset of a painful, erythematous, spreading rash with well-demarcated edges (Figure 3). There are often systemic features (e.g. fever, malaise, chills), which may precede the onset of skin lesions, and bacteraemia occurs in <5% of patients. Historically, erysipelas typically affected the face and was caused by group A streptococci.8 However, a shift in the distribution and aetiology of the disease has occurred, with most erysipelas infections now occurring on the lower extremities, and with non-group A streptococci being increasingly identified as the causative agents. Recently, atypical forms, caused by Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Yersinia enterocolitica, and Moraxella spp., have been described. Predisposing factors include skin conditions (e.g. eczema, ulcers, dermatophyte infections), venous stasis, paraparesis, diabetes, nephrotic syndrome, alcohol abuse and immunodeficiency). Erysipelas tends to occur in areas of lymphatic obstruction and, because it also causes lymphatic obstruction, tends to recur. Treatment is with intravenous benzylpenicillin. In penicillinallergic patients clindamycin may be used instead. Anti-staphylococcal therapy (flucloxacillin or vancomycin) is not usually considered necessary unless patients fail to improve with penicillin or have features suggestive of staphylococcal infection (e.g. bullous erysipelas).
Figure 4 Cellulitis of the lower limb.
Cellulitis area that is not as well demarcated or elevated as in erysipelas. Thrombophlebitis, lymphangitis, regional lymphadenopathy and fever are common. Local abscesses may develop and the overlying skin can become necrotic. The diagnosis of cellulitis is almost entirely clinical; skin swabs are unhelpful and blood cultures, skin biopsies and tissue aspirates are seldom positive. Patients with mild cellulitis and no systemic symptoms can be treated with oral or intravenous flucloxacillin; clindamycin is an alternative in penicillin-allergic patients. If the patient is diabetic or has leg ulcers, Gram-negative organisms and anaerobes are more likely, so intravenous co-amoxiclav may be used instead. Intravenous vancomycin should be used for cellulitis in patients who are known to be MRSA colonized. Teicoplanin or linezolid are suitable alternatives. Analgesia, elevation of the limb and subcutaneous heparin are useful adjunctive measures. A surgical opinion should be sought if there is circumferential cellulitis or necrotic skin.
Cellulitis is rapidly spreading inflammation of the deep dermis and subcutaneous fat (Figure 4). The most common pathogens are S. aureus and group A streptococci.9 Cellulitis caused by CA-MRSA is becoming increasingly common2 and has been reported in sports teams.10,11 Rarer causes include groups B, C and G streptococci, S. pneumoniae, Enterobacteriaceae, Pseudomonas spp., Pasteurella multocida (associated with animal contact), Aeromonas hydrophila and Vibrio vulnificus (associated with freshwater and salt water contact respectively). Cellulitis generally occurs after injury to the skin or as a result of breaches of the skin (e.g. ulcers, eczema, psoriasis, tinea infections). Patients with diabetes, leg ulcers, lymphoedema, varicose veins or peripheral vascular disease are at increased risk. Cellulitis usually affects the legs and presents as a red, hot, swollen, tender
Bursitis Bursitis is an inflammation of a bursa which may be caused by repetitive use, trauma, gout, rheumatoid arthritis, or infection (septic bursitis). Septic bursitis occurs from direct inoculation of micro-organisms through the skin or spread from adjacent cellulitis; rarely it may occur as a result of haematogenous spread. S. aureus is the predominant cause followed by streptococci and, rarely, mycobacteria or fungi. Predisposing factors include trauma, skin diseases, diabetes, alcoholism, and corticosteroid therapy. The diagnosis is clinical and based on fever plus swelling, erythema and tenderness over the affected bursa. The most common sites are the olecranon and pre-patellar bursa. Treatment is with intravenous flucloxacillin, elevation of the limb and, if necessary, aspiration of pus from the affected bursa.
Figure 3 Erysipelas caused by group A streptococcus.
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type of animal and status (behaviour, health, rabies vaccination) circumstances surrounding the bite (e.g. provoked or unprovoked) location of bite (most often on face or upper extremities) pre-hospital treatment patient’s medical history (e.g. diabetes, immunocompromised, tetanus and rabies vaccination status). Wounds on the extremities should be assessed carefully for evidence of damage to joints, muscles, tendons, nerves and blood vessels. Specialist surgeons should be consulted for wounds involving the face or hands. Prophylactic co-amoxiclav has been shown to be effective. Treatment involves copious wound irrigation, debridement, elevation of the affected part and, if appropriate, tetanus and rabies immunization. Primary wound closure is usually undertaken only for facial wounds. Magnetic resonance imaging (MRI) should be performed if there is clinical suspicion of osteomyelitis. Human bites should be managed with prophylactic antibiotics, but the risk of blood-borne viral infections should be considered. Recipients of monkey bites should be given prophylactic valaciclovir or aciclovir because of the risk of simian herpes virus B.
In penicillin-allergic or MRSA-colonized patients, vancomycin is appropriate. Surgical drainage is rarely required.
Surgical-site infections Although the prevalence of surgical site infections (SSIs) has reduced with the use of antibiotic prophylaxis, they continue to be an important cause of hospital-acquired infection. Several factors are known to contribute to the risk of SSI: host (age, nutritional status, immune status, perioperative conditions, e.g. blood glucose, body temperature and oxygenation) surgical (type of procedure, surgical technique, use of foreign material) microbial (concentration and virulence of organisms, resistance to antimicrobial prophylaxis). SSIs can be divided into three types: superficial incisional (involving skin or subcutaneous tissues); deep incisional (involving fascia or muscle); and organ/space infection. The infecting organisms are usually the patient’s endogenous flora. S. aureus (including MRSA), coagulase-negative staphylocci and enterococci are the most common organisms. However, depending of the site of surgery (e.g. gastrointestinal), Enterobacteriaceae, anaerobes and Candida spp. may be implicated. Most superficial incisional SSIs present within days after the operation, with fever and local pain, swelling, erythema, tenderness, a purulent discharge or wound dehiscence. Ultrasonography or computed tomography (CT) may be required to identify deep incisional SSI in patients with clinical evidence of systemic infection but no local signs. Management of surgical wound infection primarily involves incision and drainage, debridement of any necrotic tissue, removal of any foreign material, and local wound care. A deep pus or tissue sample should be sent for microbiological examination. Surface swabs are not useful because they merely reflect colonizing organisms. Most superficial wound infections do not require any further therapy. The need for antimicrobial therapy should be guided by clinical findings (e.g. spreading cellulitis, systemic symptoms). The initial choice of antimicrobial agent should be directed towards the most likely organisms, according to the type of operation performed. Treatment can then be tailored in light of microbiological findings. Most incisional surgical wound infections are left open and allowed to heal by secondary intention.
Infections in intravenous drug-users Intravenous drug-users often introduce bacteria into normally sterile sites. Although septicaemia and endocarditis are the greatest dangers, skin and soft tissue infections are more common (Figure 5).13 The most common organism is S. aureus, but oral flora (e.g. a-haemolytic streptococci, Neisseria spp., Haemophilus spp. and Eikenella corrodens) may be found in those who lick their needles. Other causes include S. pneumoniae, Gram-negative bacteria, Clostridia spp. and fungi. In 2000 a high fatality outbreak of SSTI occurred in the UK due to heroin contaminated with Clostridium novyi.14 Cellulitis or abscesses might occur at the site of injection and can cause considerable soft tissue damage. Injections might also
Bite infections Bite wounds are usually caused by domestic pets, e.g. dogs (most common), cats, rabbits, guinea pigs, reptiles and occasionally monkeys. It is estimated that 3e18% of dog wounds and 28e 80% of cat wounds become infected. Although most attention has focused on Pasteurella multocida, a wide spectrum of organisms has been isolated from bite wounds (e.g. staphylococci, streptococci, enterococci, Neisseria spp., Haemophilus spp., Eikenella spp., Enterobacteriaceae, Capnocytophaga canimorsus, and anaerobes).12 Human bite infections are usually associated with oral flora. Assessment for animal bite infections should include the following:
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Figure 5 Injection abscess in an intravenous drug-user.
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cause intramuscular abscesses (pyomyositis) or necrotizing fasciitis. Complications include bacteraemia, septic arthritis, osteomyelitis and infectious endocarditis. Treatment is with intravenous antibiotics and, usually, surgical drainage or debridement.
assessing the need for further surgery. Adjunctive therapies such as intravenous immunoglobulin and hyperbaric oxygen have been advocated.
Necrotizing fasciitis
Fournier’s gangrene is a form of necrotizing fasciitis that affects the genital, perineal and perianal regions. Most cases occur in patients aged 30e60 years and there is a 10:1 male to female ratio. Risk factors include advanced age, diabetes, alcohol abuse, colorectal disease/surgery, malignancy, malnutrition and immunosuppression. Men who have sex with men may be at higher risk, especially for infections caused by CA-MRSA. Fournier’s gangrene is a polymicrobial infection caused by a mixture of aerobic (e.g. Enterobacteriaceae, streptococci, enterococci, Pseudomonas spp.), and anaerobic (e.g. Bacteroides spp., Clostridium spp.) bacteria. The incidence of MRSA infections appears to be increasing. Symptoms usually begin with the insidious onset of pruritus and discomfort in the external genitalia. This is followed by swelling and erythema of the genital/perineal region and associated with severe pain and systemic symptoms. Fournier’s gangrene, like necrotizing fasciitis in other settings, is a surgical emergency that requires prompt surgical debridement and broad-spectrum intravenous antibiotic therapy (e.g. coamoxiclav, metronidazole and gentamicin). Vancomycin should be given if the patient is known or likely to be MRSA colonized. Consider a tetanus booster if immunization status is unknown e there have been cases of fatal tetanus associated with Fournier’s gangrene.
Fournier’s gangrene
Necrotizing fasciitis is an uncommon severe infection that results in destruction of subcutaneous tissue and fascia (Figure 6). Predisposing factors include diabetes, alcoholism and intravenous drug use. There are two clinical types: Type I necrotizing fasciitis is a mixed infection caused by streptococci, Enterobacteriaceae, Bacteroides spp., and Peptostreptococcus spp. It occurs in middle-aged and elderly individuals, most commonly after surgical procedures, and in those with diabetes or peripheral vascular disease. Infection usually starts in the feet and progresses rapidly along the fascia into the leg. Clinical presentation is with cellulitis and systemic signs of severe infection. Type I necrotizing fasciitis may also develop in the head and neck following a breach of the mucous membranes by surgery or instrumentation. Type II necrotizing fasciitis is caused by group A streptococci8 and was previously termed ‘streptococcal gangrene’. It may occur in any age group. The cardinal symptom is excruciating pain with minimal cutaneous findings. Initially, there may also be fever, malaise, myalgia and diarrhoea. After 24e48 h, erythema may develop, the skin may darken to a reddish-purple colour and bullae may develop. Patients are systemically unwell and may develop streptococcal toxic shock syndrome. CA-MRSA is increasingly recognized as a cause of necrotizing fasciitis in the USA.15 MRI might show subcutaneous and fascial oedema in addition to gas in the tissues. However, imaging must not delay prompt surgical exploration in patients in whom the diagnosis is clearly suspected. Necrotizing fasciitis is a surgical emergency and requires prompt surgical debridement. Intravenous broad-spectrum antibiotics (e.g. co-amoxiclav, clindamycin and gentamicin) are given until microbiological data are available. Clindamycin has a theoretical advantage in that it may interrupt toxin production and reduce systemic toxic effects. Patients often require intensive care. Imaging studies may be helpful for monitoring progress and
Gas gangrene Gas gangrene and clostridial myonecrosis are terms used to describe a rare infection caused by toxin-producing clostridia. Clostridium perfringens is the predominant cause, although other clostridial and non-clostridial species have been implicated. It is usually associated with contamination of traumatic or surgical wounds with clostridia, which then multiply in anaerobic conditions and produce exotoxins that result in tissue damage. Clinical features include the sudden onset of pain 6e8 h after injury. This is followed by increasing pain and tenderness, darkening of the skin to a purplish-red colour, formation of bullae, crepitus, fever, shock, haemolytic anaemia, liver and renal failure. Gas in the soft tissues may be confirmed by plain radiography, CT or MRI. The diagnosis is confirmed by demonstration of Gram-positive rods in the affected tissue. Management is with aggressive surgical debridement combined with intravenous antibiotics (e.g. penicillin and clindamycin). Intensive care support and multiple debridements may be required. The use of adjuvant therapies (e.g. recombinant human activated protein C, hyperbaric oxygen) is controversial.
Uncommon infections Bacterial Anthrax is caused by Bacillus anthracis and most commonly affects the skin, resulting in a ‘malignant pustule’. Infections occur in abattoir workers and result from inoculation of
Figure 6 Necrotizing fasciitis affecting the buttock.
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Parasitic Cutaneous larva migrans occurs in returning travellers, particularly those who have visited tropical beaches. It is caused by infection with animal hookworm larvae such as Ancylostoma brasiliense, Ancylostoma caninum and Uncinaria stenocephala, and presents as an itchy cluster of lesions or a sinuous track on exposed areas. Treatment is with albendazole. Leishmaniasis e cutaneous leishmaniasis is acquired from a sandfly bite. ‘Old world’ leishmaniasis, caused by Leishmania major, Leishmania tropica and Leishmania aethiopica, is endemic in Africa, Asia, India, the Middle East and the Mediterranean. ‘New world’ leishmaniasis, caused by Leishmania brasiliensis, Leishmania mexicana and Leishmania panamensis, is endemic in Latin America. Clinical presentation is with a crusted sore on the face, hand or leg 6e8 weeks after returning from an endemic area. Diagnosis is clinical and confirmed histologically. Lesions often resolve spontaneously, but some may require cryotherapy or treatment with pentavalent antimony, amphotericin or pentamidine. Patients with L. brasiliensis should be treated to avoid the possibility of espundia (mucocutaneous disease).
bacterial spores into skin abrasions caused by handling the hides of infected animals. After a few days, a papule forms at the site of infection; this develops into a vesicle and ulcerates to form a necrotic centre or eschar. Local oedema, painful regional lymphadenopathy and systemic features are often present. The diagnosis is confirmed by demonstrating Gram-positive bacilli in the ulcer fluid or tissues and by culturing the organism. Penicillin therapy is adequate, though quinolones and tetracyclines are also effective. An anthrax vaccine is available for military use. Cat-scratch disease e Bartonella henselae is the most common cause. Clinical features include regional lymphadenopathy, fever and a red papule at the inoculation site. Atypical presentations include Parinaud’s ocular glandular syndrome, maculopapular rash, erythema multiforme, erythema nodosum and leucocytoclastic vasculitis. The diagnosis is confirmed serologically and by polymerase chain reaction analysis. Treatment is with azithromycin or doxycycline. Erysipeloid is a rare condition is caused by Erysipelothrix rhusiopathiae. It is usually acquired from infected animals, and affects veterinary surgeons, farmers and butchers. The organism is inoculated into the skin and causes characteristic dark, purplish lesions with swelling of the digits. Rarely, septicaemia occurs and may be complicated by endocarditis. The condition is treated with penicillin. Erythema chronicum migrans is the cutaneous manifestation of Lyme disease, which is caused by Borrelia burgdorferi. It is acquired by inoculation from a tick bite. A red, circular lesion develops and spreads from the site of the bite. Other features include fever, malaise and arthralgia. Diagnosis is serological. Treatment is with doxycycline. Tick typhus e African tick typhus, caused by Rickettsia conorii and Rickettsia africae is commonly seen in patients returning from safari in southern Africa. Endemic typhus is caused by Rickettsia typhi and transmitted by the rat flea. Epidemic typhus is caused by Rickettsia prowazekii and transmitted by the human louse. Clinical features include fever, headache, malaise, myalgia, lymphadenopathy and splenomegaly. There may be an eschar at the site of inoculation and a maculopapular rash, though some spotted fevers produce few if any spots. Diagnosis is confirmed serologically. Treatment is with doxycycline.
Viral Herpes zoster or shingles is caused by reactivation of varicella-zoster virus infection and is characterized by a painful, vesicular eruption in a dermatomal distribution. Risk factors include increasing age, immunosuppression (e.g. transplantation, HIV infection, corticosteroid therapy) and autoimmune disease. Complications include post-herpetic neuralgia, secondary bacterial skin infection, herpes zoster opthalmicus, Ramsay Hunt syndrome (herpes zoster oticus), aseptic meningitis. Treatment is with oral valaciclovir (for uncomplicated zoster) or intravenous acyclovir for immunocompromised patients or those with ocular involvement. Herpetic whitlow (herpes simplex infection of the skin) occurs as a complication of oral or genital herpes simplex virus infection. It is characterized by a painful, erythematous vesicular or pustular skin lesion. There may be associated fever and lymphadenopathy. The diagnosis is based on exposure history. Herpetic whitlow usually resolves spontaneously in 2e3 weeks but some recommend treatment with oral acyclovir. Molluscum contagiosum is a benign condition caused by a pox virus. It usually affects children or the immunocompromised (e.g. HIV-infected patients). The lesions are most commonly seen on the face and trunk, and are papular with a central punctum. Orf is an infectious cutaneous lesion caused by a pox virus acquired from sheep. It commonly affects farmers (particularly those who bottle-feed lambs) and veterinary surgeons. A red papule develops, commonly on the sides of the fingers, and grows rapidly, often becoming vesicular, before developing a central necrotic area. Lymphangitis, regional lymphadenopathy and fever are common. Recovery is spontaneous.
Mycobacterial Leprosy e infection with Mycobacterium leprae causes a spectrum of clinical disease ranging from tuberculoid to lepromatous leprosy. In tuberculoid leprosy, anaesthetic macules or plaques, pigmentary change and thickened peripheral nerves develop. In lepromatous leprosy, macules, papules, nodules and ulceration occur, resulting in collapse of the nasal bones and coarsening of facial tissues, producing the characteristic ‘leonine’ facies. The diagnosis is confirmed by biopsy and split-skin smears. Treatment is with dapsone, clofazimine and rifampicin. Lupus vulgaris is a cutaneous infection caused by M. tuberculosis. It most commonly affects the face and neck, and appears as firm, translucent, yellow-brown ‘apple jelly’ nodules. Untreated lesions spread, leading to disfiguring scarring and contractures. Diagnosis is confirmed by biopsy, which shows tuberculoid granulomata in the mid-dermis. Treatment is with antituberculous chemotherapy.
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Ectoparasites Scabies is a pruritic skin lesion caused by infestation with Sarcoptes scabei. It is associated with poor socioeconomic conditions and overcrowding. The female mite lays her eggs in
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10 Begier EM, Frenette K, Barrett NL, et al. A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis 2004; 39: 1446e53. 11 Kazakova SV, Hageman JC, Matava M, et al. A clone of methicillinresistant Staphylococcus aureus among professional football players. N Engl J Med 2005; 352: 468e75. 12 Brook I. Microbiology and management of human and animal bite wound infections. Prim Care 2003; 30: 25e39. v. 13 Ebright JR, Pieper B. Skin and soft tissue infections in injection drug users. Infect Dis Clin North Am 2002; 16: 697e712. 14 Jones JA, Salmon JE, Djuretic T, et al. An outbreak of serious illness and death among injecting drug users in England during 2000. J Med Microbiol 2002; 51: 978e84. 15 Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 2005; 352: 1445e53.
a burrow in the stratum corneum, generating a local hypersensitivity reaction; when the eggs hatch, the cycle is repeated. Diagnosis is confirmed by extraction of the mite from a burrow. Treatment comprises topical acaricides (e.g. permethrin) and washing of all clothing and linen. All members of the household should be treated at the same time. So-called Norwegian scabies is a severe form with extensive crusting, most commonly seen in HIV infection. A
REFERENCES 1 Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005; 41: 1373e406. 2 King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and softtissue infections. Ann Intern Med 2006; 144: 309e17. 3 Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666e74. 4 Greene SL, Su WP, Muller SA. Pseudomonas aeruginosa infections of the skin. Am Fam Physician 1984; 29: 193e200. 5 Gregory DW, Schaffner W. Pseudomonas infections associated with hot tubs and other environments. Infect Dis Clin North Am 1987; 1: 635e48. 6 Nervi SJ, Schwartz RA, Dmochowski M. Eosinophilic pustular folliculitis: a 40 year retrospect. J Am Acad Dermatol 2006; 55: 285e9. 7 Duvic M. EGFR inhibitor-associated acneiform folliculitis: assessment and management. Am J Clin Dermatol 2008; 9: 285e94. 8 Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334: 240e5. 9 Swartz MN. Clinical practice. Cellulitis. N Engl J Med 2004; 350: 904e12.
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Practice points C
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Skin and soft tissue infections remain a common clinical problem The diagnosis is predominantly based on clinical features Patients with systemic features should be admitted for evaluation Empirical therapy should be targeted against the most likely infecting organism(s) and targeted in the light of microbiological data Urgent surgical debridement may be required for certain infections
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