Content » Vol 100, April

Review

Skin Infections Caused by Staphylococcus aureus

Pascal del Giudice

Infectiology-Dermatology Unit, Hospital of Fréjus-Saint-Raphaël, Fréjus, France

ABSTRACT

Staphylococcus aureus is the most common pathogen involved in skin infections worldwide, regardless of the patient’s age, the climate or geographical area. The main skin clinical manifestations can be linked to a few toxins produced by the bacteria, which give rise to a rich and varied clinical spectrum. Panton Valentine leucocidin, exfoliatins, enterotoxins and toxin shock syndrome toxin 1  are the main toxins involved in most dermatological manifestations associated with S. aureus. Other less frequent cutaneous manifestations can occur in endocarditis, bacteraemia. Currently, the most important event is worldwide emergence of community-acquired S. aureus resistant to methicillin (CA-MRSA), mainly causing skin infections.

Key words: skin infections; staphylococcus aureus; bacterial skin infections; cellulitis; furuncle; abscess.

Accepted Mar 19, 2020; Epub ahead of print Mar 24, 2020

Acta Derm Venereol 2020; 100: adv00110.

Corr: Pascal del Giudice, Service Infectiologie-Dermatologie- Centre Hospitalier Intercommunal Fréjus-Saint-Raphaël, 240 Avenue de Saint Lambert, FR-83600, Fréjus, France. E-mail: del-giudice-p@chi-fsr.fr

SIGNIFICANCE

This review describes the characteristics of Staphylococcus aureus infections of the skin. Most can be linked to a few toxins produced by the bacteria, which give rise to specific clinical manifestations. Panton Valentine leucocidin, exfoliatins, enterotoxins and toxin shock syndrome toxin 1 are the main toxins involved in most dermatological manifestations associated with Staphylococcus aureus. Unfortunately, most reports of Staphylococcus aureus skin infections do not consider this complexity. This review should help further research into Staphylococcus aureus infections of the skin to consider this rich and varied clinical spectrum.

INTRODUCTION

Staphylococcus aureus is the most common pathogen involved in skin infections worldwide, regardless of the patient’s age, the climate or geographical area. The main skin clinical manifestations can be linked to a few toxins produced by the bacteria. Panton Valentine leucocidin (PVL), exfoliatins (ETs), enterotoxins and toxin shock syndrome toxin 1 (TSST-1) are the main toxins involved in most dermatological manifestations associated with S. aureus. Other less frequent cutaneous manifestations can occur in the context of bacteraemia. The complex role of S. aureus in atopic dermatitis is not considered in this review. Currently, the most important event is the worldwide emergence of community-acquired S. aureus resistant to methicillin (CA-MRSA), which is mainly responsible for skin infections.

LOCALIZED S. AUREUS SKIN INFECTIONS

Localized S. aureus skin infections are either primary or secondary. A primary or “spontaneous” cutaneous infection is an infection occurring without preceding clinically evident lesions or secondary to a minimal skin lesion. These infections include impetigo, folliculitis, furuncles, and primary abscesses. Secondary skin infections are those occurring as a consequence of a pre-existing cutaneous lesion (usually incorrectly called “superinfections”). These include impetiginization, secondary abscesses, lymphangitis, cellulitis and secondary wound infection. This distinction between primary and secondary infection is not strict and may appear somewhat theoretical or artificial, but it allows an understanding of the physiopathology of skin infections.

Impetigo

Impetigo is an epidermal infection caused by S. aureus, Streptococcus pyogenes, or a combination of both. In northern countries S. aureus infections are predominant, representing 90% of the bacterial causes, whereas in developing countries S. pyogenes is reported to be predominant (1–5). Impetigo mainly affects children and predominates in underprivileged communities (1–5). It is contagious, with the possibility of self-inoculation and the occurrence of small family or community outbreaks.

The diagnosis of impetigo is clinical. For S. aureus impetigo, the primary lesion is a fragile bullae. The bullae quickly becomes inflamed and pustular and ruptures to form an oozing erosion or crust (Fig. 1). A frequent and typical localization in children is around the mouth, but any area of the skin can be affected. The grouping of multiple lesions can result in polycyclic erosions with circular contours. The general physical state is preserved. There is no fever; sometimes a satellite lymphadenopathy may be present. Several classical variants have been reported, such as giant impetigo, miliary impetigo, pustules, and dry impetigo. Impetigo neonatorum, previously known as pemphigus neonatorum, is generalized impetigo in neonates. Impetiginization characterizes the secondary infection by S. aureus of a pre-existing dermatosis, usually affecting the epidermis (e.g. eczema, chickenpox, etc.) or secondary to scratching (e.g. pediculosis, scabies, etc.) that results in impetigo or impetigo-like crusted and oozing lesions. A clinical variant of impetigo is ecthyma, in which deep ulceration forms in the dermis (more frequently with S. pyogenes). Scabies is a major cause of impetigo in children worldwide and, more specifically, in disadvantaged populations (6–8). Mass or individual treatment of scabies results in a decrease in the prevalence of impetigo in a community (6–8).


Fig 1. Different clinical presentations of impetigo: a), large dry erosive plaque on adbomen; b) crusted and oozing erosions on the lower limb; c) bullous and oozing erosive lesions on abdomen; d) multiple dry erosions of the hand.

The pathophysiology of staphylococcal impetigo is related to the local production of exfoliatin toxins A and B (1, 9–11). The target protein of exfoliatins A and B is desmoglein 1, a desmosomal protein whose role is the cohesion between keratinocytes, and it is mainly located in the most superficial layer of the epidermis (1, 9–11). The main consequence of the action of the toxin on desmoglein 1 is rupture of keratinocyte cohesion and formation of a bullae. Although bullae are not usually reported in impetigo caused by S. pyogenes, a similar mechanism could be involved; the streptococcal pyrogenic exotoxin B (SpeB) has been demonstrated to be a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3 (12).

According to Koning et al. (13) treatment with topical mupirocin and topical fusidic acid are equally effective to, or more effective than, oral treatment, except in extensive impetigo where research is lacking. Penicillin was not as effective as most other antibiotics (12, 13). Hygiene measures, such as strict attention to handwashing, must be applied to prevent recurrence and cross-transmission.

Regarding the risk of antibiotic resistance in impetigo, rare clones of methicillin-resistant S. aureus (MRSA) producing ETA and/or ETB and have been described, mainly from Japan (14–17). In terms of resistance in impetigo, the main concern is with fusidic acid. Resistance to fusidic acid has increased in the early 2000s in some countries of northern Europe, namely Sweden, Norway and the UK. This increase appears to have resulted from the clonal expansion of a strain designated the Epidemic European Fusidic acid resistant Impetigo Clone (EEFIC), which carries the fusidic acid resistance determinant fusB on its chromosome. The high level of use of fusidic acid ointment has been linked to the emergence and spread of fusidic acid resistant S. aureus (18–20).

Folliculitis

S. aureus is responsible for the majority of cases of folliculitis (infection of the pilosebaceous follicle).

Superficial folliculitis. In this condition the infection is restricted to the superficial part of the pilosebaceous follicle (follicular ostium). Clinically it manifests as a pustule, centred on a hair associated with a peri-follicular erythema. All parts of the body with high-density hair can be affected: thighs, perineum, arms, back, eyelid (stye). Sycosis barbae (Fig. 2), whose spread is favoured by shaving, is a particular clinical form localized on the face, characterized by extensive and chronic lesions. Differential diagnoses include folliculitis caused by other microorganisms, such as dermatophytes in kerions, Candida albicans in candida folliculitis, Malassezia folliculitis, Gram-negative folliculitis, non-infectious folliculitis (including Behcet’s disease) and hidradenitis suppurativa.


Fig. 2. Sycosis barbae.

Furuncle (boil). Furuncles, or boils, are characterized by a deep and necrotizing form of folliculitis with involvement of the pilosebaceous follicle in its entirety. It presents as a painful inflammatory papule or nodule, centred around a pustule on a hair-bearing area (the hair has usually disappeared due to necrosis) (Fig. 3). Within a few days of maturation pus will form, associated with necrosis (21). A circular desquamative flange may surround the necrotic centre (22). In recent years it has been found that up to 90% of the S. aureus, isolated from furuncles in some areas produce PVL virulence factor (23–26). This leucocidin leads to local destruction of leucocytes with the formation of larger skin lesions, which respond less well to treatment and tend to recur; the organisms can also cause suppurative pneumonia.


Fig. 3. Furuncle.

The term “furuncle” has sometimes been used in the literature for skin infection caused by other bacteria, such as non-tuberculous mycobacteria (27), but, to avoid confusion, should be reserved for S. aureus infection.

A clinical variant of a furuncle is the carbuncle, defined as a cluster of furuncles. Chronic furunculosis is characterized by the repeated formation of furuncles on different parts of the body over several months (21).

Many reports of systemic infection secondary to a furuncle are reported, but this appears to be rare relative to the high frequency of furuncles. Facial malignant sta-phylococcal infection is a classically described infection, but nowadays it is an exceptionally rare complication of a peri-nasal furuncle leading to a septic facial venous thrombosis that can extend to the cavernous sinus (28).

Abscess

An abscess is a collection of pus. The abscess forms from a tender inflammatory and extremely painful erythematous nodule or plaque. After a few days of evolution, the consistency changes and become soft, indicating the formation of the collection of pus (Fig. 4). Abscesses can be primary or secondary. There is no clearly defined size in the literature for an abscess, therefore in primary abscess, the distinction between a large furuncle and a small abscess is difficult or artificial. Fever is rare, cellulitis, lymphangitis, and satellite adenopathies may be associated. The general physical state is preserved. Pus may appear after some days of spontaneous evolution, and if not drained, spontaneous skin necrosis with rupture and drainage of the pus may occur.


Fig. 4. Primary abscess.

S. aureus is by far the main infectious bacteria isolated from abscesses. The majority of primary or spontaneous abscesses are caused by S. aureus producing PVL (23, 29–31). Secondary abscesses (accidental direct inoculation, drug addiction, septic injections, etc.) are most often, but not exclusively, due to S. aureus (32).

The treatment of suppurative skin infections is based on incision and drainage. The role of antibiotics has been summarized in recent important studies. In the study by Daum et al. (33), 786 participants with a skin abscess 5 cm or less in diameter were treated by incision and drainage and were randomly assigned to receive clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or placebo for 10 days; the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants (83.1%) and 215 of 263 participants (81.7%), respectively; p = 0.73), and the cure rate in each active treatment group was higher than that in the placebo group (177 of 257 participants (68.9%), p < 0.001 for both comparisons). Among the participants who were initially cured, new infections at 1-month follow-up were less common in the clindamycin group. Talan et al. (34) compared TMP-SMX with placebo after incision and drainage of abscesses; clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the TMP-SMX group vs. 454 of 617 participants (73.6%) in the placebo group (p = 0.005). TMP-SMX was superior to placebo, resulting in lower rates of subsequent surgical drainage procedure, skin infections at new sites, and infections in household members.

Emergence of suppurative skin infection due to community-acquired methicillin-resistant S. aureus. Methicillin has been available since 1961, it was the first semi-synthetic penicillin resistant to penicillinase produced by most of S. aureus at that time (35). Its introduction was quickly followed by the appearance of MRSA (35). This resistance is linked to the synthesis of a modified penicillin-binding protein with less affinity to betalactams, PLP2a, leading to resistance to all beta-lactams (except for new cephalosporins ceftaroline and ceftobiprole). The synthesis of this PLP2a is under the control of the mecA gene, located on a chromosomal mobile genetic element, called the staphylococcal cassette chromosome mec or SCCmec, bordered at both ends by genes called chromosome cassette recombinase (ccRA/ccRB or ccRC), which allow horizontal transmission between and within species. Described almost exclusively in hospitals, these hospital-acquired methicillin-resistant (HA-MRSA), clones have spread widely throughout the world. Over time, they have acquired, in addition to the mecA gene, other resistance genes against other classes of antibiotics, such as macrolides, fluoroquinolones or aminoglycosides (1). However, these clones are rarely involved in skin infections, except for nosocomial operative site infections.

The epidemiology of MRSA has entered a new era the last 25 years. MRSA with new characteristics have emerged in the community setting, namely outside of healthcare facilities (35–39). First reported in Oceania (Australia and New Zealand), these CA-MRSA are currently present worldwide (35–39). Most strains (80–90%) are isolated from suppurative skin infections (35–39). CA-MRSA infections have specific characteristics that clearly distinguish them from HA-MRSA (35–39); they preferentially affect a young population with no previous medical history (35–39). Unlike HA-MRSA, which are often multi-resistant, CA-MRSA generally remains sensitive to most antibiotics apart from beta-lactams. The genetic origin of CA-MRSA is different, with a few major clonal complexes with relative geographical specificity (35–39), USA 300 being the major clone in the USA. The main SCCmec cassettes for HA-MRSA (SCCmec I, II and III) are significantly longer than those for CA-MRAS (mainly SCCmec IV and V). Almost all of CA-MRSA, including the major clones, produce the PVL toxin, which explains the predominance of suppurative skin infections as clinical presentations of CA-MRSA infections. There are no clinical data to suggest that PVL CA-MRSA skin infections differ from PVL methicillin-sensitive ones (MSSA) and their relative prevalence varies in different countries. As CA-MRSA is isolated mainly from suppurative skin infections, the best way to study its epidemiology is to study those infections. Indeed, some countries, such as the USA, have a high rate of CA-MRSA, at approximately 50% of strains isolated (most USA 300) (40–42) and others have a low rate, at less than 10% (43–45). Outbreaks of CA-MRSA are regularly described mainly in different community settings (military personnel, sports teams, drug users, homosexuals, isolated communities, families, etc.) (46–50).

Acute suppurative paronychia

Acute suppurative paronychia is an acute infection of the eponychial nail folds of the hand or foot. Several bacteria may be implicated, but S. aureus is the most common one. The treatment is based on surgical excision; antibiotic treatment plays a minimal role (51).

Lymphangitis

Lymphangitis is caused mainly by S. aureus or S. pyogenes. It is clinically characterized by an erythematous inflammatory linear band, which usually starts from the origin of the infection towards the draining regional lymph node, namely a local adenopathy (Fig. 5). Lym-phangitis is sometimes accompanied by fever. Otherwise, general health state is preserved. Treatment is based on systemic antibiotic therapy.


Fig. 5. Lymphangitis.

Superficial septic thrombophlebitis

An important feature in the pathophysiology of S. aureus infections is its thrombotic capacity. The constitution of a vascular thrombosis allows the infection to develop and cause septic emboli and secondary locations. Staphylococcal skin infection can cause septic thrombophlebitis of the superficial venous network, which can spread to the deep veins. In hospitals, this is most often a complication related to the infection of intravenous catheters. Septic thrombophlebitis is characterized by an inflammatory indurated cord, which begins at the infected site (Fig. 6). Treatment is based on antibiotic therapy and treatment of the portal of entry. A particular form of such thrombophlebitis is facial malignant staphylococcal infection (see above).


Fig. 6. Thrombophlebitis from catheter site.

Cellulitis

Cellulitis may occur associated with an abscess or a thrombo-phlebitis or complicate an acute or chronic wound as a result of secondary infection. It is more common with S. pyogenes. The treatment is based on systemic antibiotic therapy.

Necrotizing fasciitis

A few reports of necrotizing fasciitis (NF) associated with S. aureus have been published. Miller et al. (52) reported 14 cases in 2005 caused by CA-MRSA. A few other isolated cases have been published since. Given the scarcity of the reports, NF caused by S. aureus seems exceptional.

Contiguous infections

These are related to a suppurative focus located near the skin (53). They manifest as an inflammatory mass that simulates an abscess, particularly in the vicinity of septic arthritis, osteomyelitis, bursitis, tenosynovitis or infected false aneurysms or myositis. Sometimes cutaneous fistulization occurs.

Secondary infections of acute or chronic wounds

They are a common situation in practice. Clinically, secondary infections show local inflammatory signs (pain, erythema) or cellulitis, and the possible presence of pus (54). The isolation of S. aureus in a wound is not synonymous with local infection, but must be interpreted according to the clinical presentation and, especially, the presence of inflammatory signs. The distinction between secondary infection and colonization may be difficult.

Botryomycosis

S. aureus can cause botryomycosis, a rare, chronic and granulomatous infection characterized by painless slow-growing papulonodules, abscesses and ulcers and, histopathologically, the presence of granules composed of bacterial cocci (55).

SYSTEMIC CUTANEOUS MANIFESTATIONS DUE TO TOXIN-PRODUCING S. AUREUS

Toxic shock syndrome

The toxic shock syndrome (TSS) was first described by Todd (1978) in 7 children who had a generalized erythema, fever, hypotension, diarrhoea and multi-organ failure (56). In 1980 many cases were reported in young women who used certain types of tampon (57, 58). The incidence of menstrual TSS in the US peaked in 1980 and has decreased significantly since the removal of these tampons from the market (59).

TSS is due to the production of a toxin by S. aureus, mainly TSST-1 and staphylococcal enterotoxins, particularly enterotoxin B and, less commonly, other enterotoxins (56). The 1997 CDC definition (60) includes the following clinical criteria: fever (≥ 38.9°C) a diffuse macular erythroderma, desquamation (1–2 weeks after onset of illness, particularly on the palms and soles), hypotension, multisystem organ involvement (57). In a study of 130 TSS, Reingold et al. (57) found a skin infection in 30% of cases, a genital focus in 27% (after delivery or abortion), 18% post-surgery focus, and in 13% the source was not identified. The pathogenesis of TSS is linked to the properties of superantigens in S. aureus toxins, namely activation of greater numbers of T lymphocytes resulting in the production of high levels of cytokines (33). Skin manifestations of TSS include a generalized erythema (with palm and sole involvement) (Fig. 7). Palmar, sole and finger desquamation may occur after recovery (Fig. 8). Transient alopecia, nail shedding and increased sweating on the hands and feet have been described (61). Treatment is based on the treatment of the multi-organ failure and the S. aureus focus of infection. Some antibiotics acting as protein-synthesis inhibitors with anti-toxaemic properties could provide additional therapeutic benefits (62).


Fig. 7. Erythema of toxic shock syndrome.


Fig. 8. Distal desquamation after toxic shock syndrome.

In Japan, Takahashi et al. (63) have reported neonates who developed generalized erythema and thrombocytopaenia in the first week of life associated with MRSA-producing TSST-1. They propose neonatal toxic-shock-syndrome-like exanthematous disease (NTED) as the name for this disease. Similar cases have been reported in Europe (64).

“Staphylococcal scarlet fever”

Staphylococcal scarlet fever, also called scarlatiniform erythroderma/rash, was first described in the 1920s. Lina et al. (65) found that 16 out of 17 strains of S. aureus isolated from patients with staphylococcal scarlet fever produced TSST-1, enterotoxins, or both. Enterotoxin B was the predominant toxin involved in a study in Taiwan (66). It is possible that most cases of staphylococcal scarlet fever are, in fact, a mild or attenuated clinical manifestation of TSS.

Staphylococcal scalded skin syndrome

When the ETs spread systemically, they can cause SSSS (9–11, 67). It is a generalized blistering disease affecting mainly neonates and young children and, exceptionally, adults with underlying diseases. The disease begins abruptly with fever and generalized erythema, followed by large fragile blisters involving the entire skin surface within the next few hours to days, which rupture rapidly (with a positive Nikolsky sign) (67). Widespread involvement of the entire skin surface can occur, but the mucous membranes are usually spared. Mild forms of SSSS have been described where the SSSS is limited to the body folds associated with a fine generalized desquamation (68). The disease follows localized S. aureus infection. Poor renal clearance of the toxins by neonates and by adults with impaired renal function is a major risk factor for developing SSSS. The prognosis of SSSS in children, who are appropriately treated, is good, with a mortality of less than 5%, but it may be fatal in up to 60% of affected adults, usually due to underlying diseases (67). The diagnosis of SSSS is clinically based. Exfoliatins are produced by S. aureus at a distant site; the blister fluid in generalized SSSS is usually sterile. The treatment is based on dressings, where there are large blisters, and the eradication of the source of S. aureus infection focus.

SKIN MANIFESTATIONS OF S. AUREUS BACTERAEMIA

Skin manifestations of S. aureus endocarditis

Endocarditis caused by S. aureus is classified as acute endocarditis. The description of endocarditis-related skin manifestations is confusing; Janeway lesions and Osler’s nodes were described at the beginning of the 20th century (1). Classically reported Janeway lesions are macular, purpuric lesions that occur on hands and feet (Fig. 9). Histologically, they show neutrophilic microabscesses in the dermis and vessel thrombosis (69). These lesions are thought to be caused by septic microemboli; results of culture of skin specimens are frequently positive (70–73). Osler’s nodes are described as small, painful, nodular lesions on the fingers or toes. Only a few biopsied Osler’s nodes gave positive results on culture, and histological examination showed diverse findings (73). The description of Janeway lesions corresponds better with the skin manifestations of S. aureus endocarditis.

Skin manifestations of S. aureus bacteraemia (without endocarditis)

Such manifestations related to the frequency of S. aureus bacteraemia are extremely rare. Purpuric disseminated eruptions and abscesses are the main clinical manifestations that have been described as a secondary focus of S. aureus bacteraemia. Exceptionally, purpura fulminans has also been reported (74).


Fig. 9. Purpura during endocarditis.

IMMUNOLOGICAL SKIN MANIFESTATIONS OF S. AUREUS INFECTION

Immunological manifestations associated with acute or chronic S. aureus infections are rare. A few cases of vasculitis or Henoch-Schönlein purpura have been reported, mainly in the course of S. aureus bacteraemia (75–77). Some of these associations may be coincidental.

CONCLUSION

Staphylococcal skin infections are part of a complex group of diseases. Unfortunately, most reports in the literature classify skin infections and S. aureus skin infections under the heading “skin and skin structures infections (SSTI)”, giving the illusion that all skin manifestations are within the same clinical spectrum. This review shows, on the contrary, how the clinical spectrum of skin manifestations due to S. aureus is diverse and related to different physiopathologies. Further reports and studies on skin S. aureus infections should take into consideration this rich and varied clinical spectrum of disease.

This review has focused on the clinical and therapeutic aspects of S. aureus skin infections, and many other questions are not mentioned, such as the interactions of S. aureus with the skin microbiome, the reservoirs of S. aureus, the relationships between reservoirs and skin infections, and the decolonization of the reservoirs. All of these complex topics are currently the subject of intense research.

REFERENCES
  1. Stanley JR, Amagai M. Pemphigus, bullous impetigo and staphylococcal scald skin syndrome. N Engl J Med 2006; 355: 1800–1810.
    View article    Google Scholar
  2. Salah LA, Faergemann J. A retrospective analysis of skin bacterial colonisation, susceptibility and resistance in atopic dermatitis and impetigo patients. Acta Derm Venereol 2015; 95: 532–535.
    View article    Google Scholar
  3. Rosen T, Albareda N, Rosenberg N, Alonso FG, Roth S, Zsolt I, et al. Efficacy and safety of ozenoxacin cream for treatment of adult and pediatric patients with impetigo: a randomized clinical trial. JAMA Dermatol 2018; 154: 806–813.
    View article    Google Scholar
  4. Bowen AC, Mahé A, Hay RJ, Andrews RM, Steer AC, Tong SY, et al. The global epidemiology of impetigo: a systematic review of the population prevalence of impetigo and pyoderma. PLoS One 2015; 10: e0136789.
    View article    Google Scholar
  5. Bowen AC, Tong SY, Chatfield MD, Carapetis JR. The microbiology of impetigo in indigenous children: associations between Streptococcus pyogenes, Staphylococcus aureus, scabies, and nasal carriage. BMC Infect Dis 2014; 14: 727.
    View article    Google Scholar
  6. Engelman D, Cantey PT, Marks M, Solomon AW, Chang AY, Chosidow O, et al. The public health control of scabies: priorities for research and action. Lancet 2019; 394: 81–92.
    View article    Google Scholar
  7. Korte LM, Bowen AC, Draper ADK, Davis K, Steel A, Teodora I, et al. Scabies and impetigo in Timor-Leste: a school screening study in two districts. PLoS Negl Trop Dis 2018; 12: e0006400.
    View article    Google Scholar
  8. Romani L, Whitfeld MJ, Koroivueta J, Kama M, Wand H, Tikoduadua L, et al. Mass drug administration for scabies – 2 years of follow-up. N Engl J Med 2019; 381: 186–187.
    View article    Google Scholar
  9. Hanakawa Y. Schechter NM, Lin C, Garza L, Li H, Yamaguchi T, Fudaba Y, et al. Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome. J Clin Invest 2002; 110: 53–60.
    View article    Google Scholar
  10. Amagai M, Matsuyoshi N, Wang ZH, Andl C, Stanley JR. Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1. Nat Med 2000; 6: 1275–1277.
    View article    Google Scholar
  11. Amagai M, Yamagushi T, Hanakawa Y, Nishifuji K, Sugai M, Stanley JR. Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1. J Invest Dermatol 2002; 118: 845–850.
    View article    Google Scholar
  12. Sumitomo T, Mori Y, Nakamura Y, Honda-Ogawa M, Nakagawa S, Yamaguchi M, et al. Streptococcal cysteine protease-mediated cleavage of desmogleins is involved in the pathogenesis of cutaneous infection. Front Cell Infect Microbiol 2018; 8: 10.
    View article    Google Scholar
  13. Koning S, Van Der Sande R, Verhagen AP, Van Suijlekom-Smit LW, Morris AD, Butler CC, et al. Interventions for impetigo. Cochrane Database Syst Rev 2012; 1: CD003261.
    View article    Google Scholar
  14. Yamaguchi T, Yokota Y, Terajima J, Hayashi T, Aepfelbacher M, Ohara M, et al. Clonal association of Staphylococcus aureus causing bullous impetigo and the emergence of new methicillin-resistant clonal groups in Kansai district in Japan. J Infect Dis 2002; 185: 1511–1516.
    View article    Google Scholar
  15. Liassine N, Auckenthaler R, Descombes MC, Bes M, Vandenesch F, Etienne J. Community-acquired methicillin-resistant Staphylococcus aureus isolated in Switzerland contains the Panton-Valentine leukocidin or exfoliative toxin genes. J Clin Microbiol 2004; 42: 825–828.
    View article    Google Scholar
  16. Shi D, Higuchi W, Takano T, Saito K, Ozaki K, Takano M, et al. Bullous impetigo in children infected with methicillin-resistant Staphylococcus aureus alone or in combination with methicillin-susceptible S. aureus: analysis of genetic characteristics, including assessment of exfoliative toxin gene carriage. J Clin Microbiol 2011; 185: 1511–1516.
    View article    Google Scholar
  17. Hisata K, Ito T, Matsunaga N, Komatsu M, Jin J, Li S, et al. Dissemination of multiple MRSA clones among community-associated methicillin-resistant Staphylococcus aureus infections from Japanese children with impetigo. J Infect Chemother 2011; 17: 609–621.
    View article    Google Scholar
  18. O’Neill AJ, Larsen AR, Skov R, Henriksen AS, Chopra I. Characterization of the epidemic European fusidic acid-resistant impetigo clone of Staphylococcus aureus. J Clin Microbiol 2007; 45: 1505–1510.
    View article    Google Scholar
  19. O’Neill AJ, Larsen AR, Henriksen AS, Chopra I. A fusidic acid-resistant epidemic strain of Staphylococcus aureus carries the fusB determinant, whereas fusA mutations are prevalent in other resistant isolates. Antimicrob Agents Chemother 2004; 48: 3594–3597.
    View article    Google Scholar
  20. Williamson DA, Monecke S, Heffernan H, Ritchie SR, Roberts SA, Upton A, et al. High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale. Clin Infect Dis 2014; 59: 1451–1454.
    View article    Google Scholar
  21. Demos M, McLeod MP, Nouri K. Recurrent furunculosis: a review of the literature. Br J Dermatol 2012; 167: 725–732.
    View article    Google Scholar
  22. Levy AL, Simpson G, Skinner RB Jr. Medical pearl: circle of desquamation – a clue to the diagnosis of folliculitis and furunculosis caused by Staphylococcus aureus. J Am Acad Dermatol 2006; 55: 1079–1080.
    View article    Google Scholar
  23. Couppie P, Cribier B, Prevost G. Leukocidin from Staphylococcus aureus and cutaneous infections: an epidemiologic study. Arch Dermatol 1994; 130: 1208–1209.
    View article    Google Scholar
  24. Del Giudice P, Bes M, Hubiche T, Blanc V, Roudière L, Lina G, et al. Panton-Valentine leukocidin-positive Staphylococcus aureus strains are associated with follicular skin infections. Dermatology 2011; 222: 167–170.
    View article    Google Scholar
  25. Baba-Moussa L, Sina H, Scheftel JM, Moreau B, Sainte-Marie D, Kotchoni SO, et al. Staphylococcal Panton-Valentine leucocidin as a major virulence factor associated to furuncles. Plos One 2011; 6: e25716.
    View article    Google Scholar
  26. Yamasaki O, Kaneko J, Morizane S, Akiyama H, Arata J, Narita S, et al. The Association between Staphylococcus aureus strains carrying Panton-Valentine leukocidin genes and the development of deep-seated follicular infection. Clin Infect Dis 2005; 40: 381–385.
    View article    Google Scholar
  27. Winthrop KL, Abrams M, Yakrus M, Schwartz I, Ely J, Gillies D, et al. An outbreak of mycobacterial furunculosis associated with footbaths at a nail salon. N Engl J Med 2002; 34: 1366–1371.
    View article    Google Scholar
  28. Kramkimel N, Sbidian E, Duong TA, Lesprit P, Roujeau JC, Bagot M. Septic facial vein thrombosis due to Panton-Valentine leukocidin-positive Staphylococcus aureus. Arch Dermatol 2009; 145: 1460–1461.
    View article    Google Scholar
  29. Del Giudice P, Blanc V, De Rougemont A, Hubiche T, Roudière L, Bes M, et al. J. Panton-Valentine leukocidin positive Staphylococcus aureus strains cause primary skin abscesses. Dermatology 2009; 219: 299–302.
    View article    Google Scholar
  30. Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V et. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis 1999; 29: 1128–1132.
    View article    Google Scholar
  31. Issartel B, Tristan A, Lechevallier S, Bruyère F, Lina G, Garin B, et al. Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses. J Clin Microbiol 2005; 43: 3203–3207.
    View article    Google Scholar
  32. Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015; 372: 1093–1103.
    View article    Google Scholar
  33. Daum RS, Miller LG, Immergluck L, Fritz S, Creech CB, Young D, et al. A placebo-controlled trial of antibiotics for smaller skin abscesses. N Engl J Med 2017; 376: 2545–2555.
    View article    Google Scholar
  34. Talan DA, Mower WR, Krishnadasan A, Abrahamian FM, Lovecchio F, Karras DJ, et al. Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med 20; 374: 823–832.
    View article    Google Scholar
  35. Lowy FD. Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest 2003; 111: 1265–1273.
    View article    Google Scholar
  36. Deleo FR, Otto M, Kreiswirth BN, Chambers HF. Community-associated meticillin-resistant Staphylococcus aureus. Lancet 2010; 375: 1557–1568.
    View article    Google Scholar
  37. Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, et al. Comparison of community and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003; 290: 2976–2984.
    View article    Google Scholar
  38. Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, Heffernan H, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 2003; 9: 978–984.
    View article    Google Scholar
  39. Tristan A, Bes M, Meugnier H, Lina G, Bozdogan B, Courvalin P, et al. Global distribution of Panton-Valentine leukocidin – positive methicillin-resistant Staphylococcus aureus, 2006. Emerg Infect Dis 2007; 13: 594–600.
    View article    Google Scholar
  40. King MD, 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 soft-tissue infections. Ann Intern Med 2006; 144: 309–317.
    View article    Google Scholar
  41. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et al. Methicillin-resistant Staphylococcus aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666–674.
    View article    Google Scholar
  42. Talan DA, Krishnadasan A, Gorwitz RJ, Fosheim GE, Limbago B, Albrecht V, Moran GJ; EMERGEncy ID Net Study Group. Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin Infect Dis 2011; 53: 144–149.
    View article    Google Scholar
  43. Del Giudice P, Blanc V, Durupt F, Bes M, Martinez JP, Counillon E, et al. Emergence of two populations of methicillin-resistant Staphylococcus aureus with distinct epidemiological, clinical and biological features, isolated from patients with community-acquired skin infections. Br J Dermatol 2006; 154: 118–124.
    View article    Google Scholar
  44. Jappe U, Heuck D, Strommenger B, Wendt C, Werner G, Altmann D, Witte W. Staphylococcus aureus in dermatology outpatients with special emphasis on community-associated methicillin-resistant strains. J Invest Dermatol 2008; 128: 2655–2664.
    View article    Google Scholar
  45. Deplano A, Dodémont M, Denis O, Westh H, Gumpert H, Larsen AR, et al. F. European external quality assessments for identification, molecular typing and characterization of Staphylococcus aureus. J Antimicrob Chemother 2018; 73: 2662–2666.
    View article    Google Scholar
  46. Fridkin SK, Hageman JC, Morrison M, Sanza LT, Como-Sabetti K, Jernigan JA, et al. Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005; 352: 1436–1444.
    View article    Google Scholar
  47. Young DM, Harris HW, Charlebois ED, Chambers H, Campbell A, Perdreau-Remington F, et al. An epidemic of methicillin-resistant Staphylococcus aureus soft tissue infections among medically underserved patients. Arch Surg 2004; 139: 947–951; discussion 951–953.
    View article    Google Scholar
  48. Huijsdens XW, van Santen-Verheuvel MG, Spalburg E, Heck ME, Pluister GN, Eijkelkamp BA, et al. Multiple cases of familial transmission of community-acquired methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2006; 44: 2994–2996.
    View article    Google Scholar
  49. Lee NE, Taylor MM, Bancroft E, Ruane PJ, Morgan M, McCoy L, et al. Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men. Clin Infect Dis 2005; 40: 1529–1534.
    View article    Google Scholar
  50. Diep BA, Chambers HF, Graber CJ, Szumowski JD, Miller LG, Han LL, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med 2008; 148: 249–257.
    View article    Google Scholar
  51. Pierrart J, Delgrande D, Mamane W, Tordjman D, Masmejean EH. Acute felon and paronychia: Antibiotics not necessary after surgical treatment. Prospective study of 46 patients. Hand Surg Rehabil 2016; 35: 40–43.
    View article    Google Scholar
  52. Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS, Tang AW, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 2005; 352: 1445–1453.
    View article    Google Scholar
  53. Del Giudice P. Contiguous cutaneous inflammation: different scenarios, unclear outlines. Ann Dermatol Venereol 2018; 145: 561–562.
    View article    Google Scholar
  54. Reddy M, Gill SS, Wu W, Kalkar SR, Rochon PA. Does this patient have an infection of a chronic wound? JAMA 2012; 307: 605–611.
    View article    Google Scholar
  55. Ingen-Housz-Oro S, Leprince P, Ortonne N, Cluzel P, Gautier MS, Wolkenstein P et al Nodules on a sternotomy scar. Lancet Infect Dis 2015; 15: 986.
    View article    Google Scholar
  56. Todd J. Toxic shock syndrome. Clin Microbiol Rev 1988; 1: 432–446.
    View article    Google Scholar
  57. Reingold AL, Hargrett NT, Dan BB, Shands KN, Strickland BY, Broome CV. Non menstrual toxic shock syndrome: a review of 130 cases. Ann Intern Med 1982; 96: 871–874.
    View article    Google Scholar
  58. Broome CV, Hayes PS, Ajello GW, Feeley JC, Gibson RJ, Graves LM, et al. In-vitro studies of interactions between tampons and Staphylococcus aureus. Ann Intern Med 1982; 96: 959–962.
    View article    Google Scholar
  59. Hajjeh RA, Reingold A, Weil A, Shutt K, Schuchat A, Perkins BA. Toxic shock syndrome in the United States: surveillance update, 1979 1996. Emerg Infect dis 1999; 5: 807–810.
    View article    Google Scholar
  60. Toxic shock syndrome. Available from: https://www.cdc.gov/nndss/conditions/toxic-shock-syndrome-other-than-streptococcal/case-definition/2011/.
    View article    Google Scholar
  61. Crowther MA, Ralph ED. Menstrual toxic shock syndrome complicated by persistent bacteremia: case report and review. Clin Infect Dis 1993; 1: 288–289.
    View article    Google Scholar
  62. Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis 2007; 195: 202–211.
    View article    Google Scholar
  63. Takahashi N, Nishida H, Kato H, Imanishi K, Sakata Y, Uchiyama T. Exanthematous disease induced by toxic shock syndrome toxin 1 in the early neonatal period. Lancet 1998; 351: 1614–1619.
    View article    Google Scholar
  64. Van Der Mee-Marquet N, Lina G, Quentin R, Yaouanc-Lapalle H, Fievre C, Takahashi N, et al. Staphylococcal exanthematous disease in a newborn due to a virulent methicillin-resistant Staphylococcus aureus strain containing the TSST-1 gene in Europe: an alert for neonatologists. J Clin Microbiol 2003; 41: 4883–4884.
    View article    Google Scholar
  65. Lina, G, Gillet Y, Vandenesch F, Jones ME, Floret D, Etienne J. Toxin involvement in staphylococcal scalded skin syndrome. Clin Infect Dis 1997; 25: 1369–1373.
    View article    Google Scholar
  66. Wang CC, Lo WT, Hsu CF, Chu ML. Enterotoxin B is the predominant toxin involved in staphylococcal scarlet fever in Taiwan. Clin Infect Dis 2004; 38: 1498–1502.
    View article    Google Scholar
  67. Ladhani S, Joannou CL, Lochrie DP, Evans RW, Poston SM. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev 1999; 12: 224–242.
    View article    Google Scholar
  68. Hubiche T, Bes M, Roudiere L, Langlaude F, Etienne J, Del Giudice P. Mild staphylococcal scalded skin syndrome: an underdiagnosed clinical disorder. Br J Dermatol 2012; 166: 213–215.
    View article    Google Scholar
  69. Parikh SK, Lieberman A, Colbert DA, Slivers DN, Grossman ME. The identification of methicillin-resistant Staphylococcus aureus in Osler’s nodes and Janeway lesions of acute bacterial endocarditis. J Am Acad Dermatol 1996; 35: 767–768.
    View article    Google Scholar
  70. Maestre A, Mora A, Gutiérrez F, Hidalgo AM, Monmeneu JV, Mirete C, López F. Diagnosis: a Janeway lesion and an Osler’s node. Clin Infect Dis 2001; 32; 63: 149.
    View article    Google Scholar
  71. Gil MP, Velasco M, Botella JE, Ballester JE, Pedro F, Aliaga A. Janeway lesions: differential diagnosis with Osler’s nodes. Int J Dermatol 1993; 32: 673.
    View article    Google Scholar
  72. Cardullo AC, Silvers D, Grossman ME. Janeway lesions and Osler’s nodes: a review of histopathologic findings. J Am Acad Dermatol 1990; 22: 1088–1090.
    View article    Google Scholar
  73. Vinson RP, Chung A, Elston DM, Keller RA. Septic microemboli in a Janeway lesion of bacterial endocarditis. J Am Acad Dermatol 1996; 35: 984–985.
    View article    Google Scholar
  74. Kravitz GR, Dries DJ, Peterson ML, Schlievert PM. Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis 2005; 40: 941–947.
    View article    Google Scholar
  75. Maliske SM, Edwards D, Suneja M. Methicillin-resistant Staphylococcus aureus-related Henoch-Schönlein purpura treated without systemic immunosuppressants. Am J Med Sci 2015; 350: 514–516.
    View article    Google Scholar
  76. Yamaguchi Y, Fujita Y, Ikeda T, Mai Y, Miyazawa H, Matsumura W, et al. Severe septic vasculitis preceding thoracic empyema: staphylococcus aureus enterotoxin deposition in vessel walls as a possible pathomechanism. Acta Derm Venereol 2019; 99: 464–465.
    View article    Google Scholar
  77. Mosher CA, Owen JL, Barker BR. Staphylococcus aureus bacteremia masquerading as leukocytoclastic vasculitis. Am J Med 2016; 129: e5–7.
    View article    Google Scholar