Microbial disease of the skin may result from any of three lines of attack

These lines of attack are:

The sequence of events in the pathogenesis of mucocutaneous lesions caused by bacterial, fungal and viral infections is outlined in Figure 26.2. Breaches in the skin range from microscopic to major trauma, which may be accidental (e.g. lacerations or burns) or intentional (e.g. surgery). Hospitalized patients are liable to other skin breaches (e.g. pressure sores and intravenous catheter insertions), which may become infected (see Ch. 36). Infections in compromised individuals such as patients with burns are discussed in Chapter 30. Here, we will consider primary infections of the skin and underlying soft tissues, together with mucocutaneous lesions resulting from certain systemic viral infections. Examples of systemic bacterial and fungal infections that cause mucocutaneous lesions are summarized in Table 26.1.

Figure 26.2 The pathogenesis of mucocutaneous lesions. In different infections, the starting point (arrival of microbe or toxin or immune complex) and the final picture (e.g. maculopapular rash, vesicle) will be different. HSV, herpes simplex virus; VZV, varicella-zoster virus.

Table 26.1 Skin manifestations of systemic infections caused by bacteria and fungi

Organism	Disease	Skin manifestation
Salmonella typhi, Salmonella schottmuelleri	Enteric fever	‘Rose spots’ containing bacteria
Neisseria meningitidis	Septicaemia, meningitis	Petechial or maculopapular lesions containing bacteria
Pseudomonas aeruginosa	Septicaemia	Ecthyma gangrenosum, skin lesion pathognomonic if infected by this organism
Treponema pallidum Treponema pertenue	Syphilis Yaws
Rickettsia prowazekii Rickettsia typhi Rickettsia rickettsii	Typhus
Streptococcus pyogenes	Scarlet fever	Erythematous rash caused by erythrogenic toxin
Staphylococcus aureus	Toxic shock syndrome	Rash and desquamation due to toxin
Blastomyces dermatitidis	Blastomycosis	Papule or pustule develops into granuloma lesions containing organisms
Cryptococcus neoformans	Cryptococcosis	Papule or pustule, usually on face or neck

Skin lesions are often associated with systemic infection with particular bacteria and fungi. The lesions may provide useful diagnostic aids. Sometimes they are a site from which organisms are shed.

These can be classified on an anatomic basis

The classification depends upon the layers of skin and soft tissue involved, although some infections may involve several components of the soft tissues:

The common causative organisms are shown in Table 26.2. Note that the same pathogen (e.g. Streptococcus pyogenes) can cause different infections in different layers of the skin and soft tissue.

Table 26.2 Direct entry into skin of bacteria and fungi

Structure involved	Infection	Common cause
Keratinized epithelium	Ringworm	Dermatophyte fungi (Trichophyton, Epidermophyton and Microsporum)
Epidermis	Impetigo	Streptococcus pyogenes and/or Staphylococcus aureus
Dermis	Erysipelas	Strep. pyogenes
Hair follicles	Folliculitis Boils (furuncles) Carbuncles	Staph. aureus
Subcutaneous fat	Cellulitis	Strep. pyogenes
Fascia	Necrotizing fasciitis	Anaerobes and microaerophiles, usually mixed infections
Muscle	Myonecrosis gangrene	Clostridium perfringens (and other clostridia)

Direct introduction of bacteria or fungi into the skin is the most common route of skin infection. Infections range from mild, often chronic, conditions such as ringworm to acute and life-threatening fasciitis and gangrene. Relatively few species are involved in the common infections.

Staphylococcus aureus is the most common cause of skin infections and provokes an intense inflammatory response

Staphylococcus aureus causes minor skin infections such as boils or abscesses as well as more serious postoperative wound infection. Infection may be acquired by ‘self-inoculation’ from a carrier site (e.g. the nose) or acquired by contact with an exogenous source, usually another person. People who are nasal carriers of virulent Staph. aureus may suffer from recurrent boils, but an inoculum of about 100 000 organisms is thought to be required in the absence of a wound or foreign body. Staph. aureus can also cause serious skin disease due to toxin production (scalded skin syndrome, toxic shock syndrome; see below). In addition, skin and soft tissue infections caused by community-associated, methicillin-resistant Staph. aureus strains (CA-MRSA) are of increasing incidence and concern (see Ch. 36).

A boil begins within 2–4    days of inoculation, as a superficial infection in and around a hair follicle (folliculitis; Fig. 26.3). In this site, the organisms are relatively protected from the host defences, multiply rapidly and spread locally. This provokes an intense inflammatory response with an influx of neutrophils. Fibrin is deposited, and the site is walled off. Abscesses typically contain abundant yellow creamy pus formed by the massive number of organisms and necrotic white cells. They continue to expand slowly, eventually erode the overlying skin, ‘come to a head’ and drain. Drainage inwards can result in seeding of the staphylococci to underlying body sites to cause serious infections such as peritonitis, empyema or meningitis.

Figure 26.3 Folliculitis. A superficial infection is shown here localized in the hair follicles on the leg. The boils contain creamy-yellow pus and masses of bacteria. Staphylococcus aureus is the most common cause.

(Courtesy of A. du Vivier.)

Staph. aureus infections are often diagnosed clinically and treatment includes drainage and antibiotics

Staph. aureus is the most common cause of boils, and diagnosis is made on clinical grounds. Isolation and further characterization of the infecting staphylococcus in hospital patients and staff are important in the investigation of hospital infections (see Ch. 36).

Treatment involves drainage and this is usually sufficient for minor lesions, but antibiotics may be given in addition when the infection is severe and the patient has a fever. Most Staph. aureus are beta-lactamase producers, but methicillin-susceptible Staph. aureus (MSSA) can be treated with enzyme-stable penicillins such as nafcillin. Isolates resistant to these compounds (i.e. methicillin-resistant Staph. aureus (MRSA); see Ch. 33) may be treated with vancomycin, linezolid, quinopristin-dalfoprisin, or daptomycin. Treatment with these agents does not necessarily eradicate carriage of the staphylococci.

Recurrent infections may be treated in nasal carriers of Staph. aureus with nasal creams containing antibiotics. For example, mupirocin has been used successfully for carriers of methicillin-resistant staphylococci (see Ch. 36). Good skin care and personal hygiene should be encouraged.

Staphylococcal scalded skin syndrome is caused by toxin-producing Staph. aureus

This condition, also known as ‘Ritter’s disease’ in infants and ‘Lyell’s disease’ or ‘toxic epidermal necrolysis’ in older children, occurs sporadically and in outbreaks. It is caused by strains of Staph. aureus producing a toxin known as ‘exfoliatin’ or ‘scalded skin syndrome toxin’. The initial skin lesion may be minor, but the toxin causes destruction of the intercellular connections and separation of the top layer of the epidermis. Large blisters are formed, containing clear fluid, and within 1 or 2    days, the overlying areas of skin are lost (Fig. 26.4), leaving normal skin underneath. The baby is irritable and uncomfortable, but rarely severely ill. However, treatment should take into account the risk of increased loss of fluid from the damaged surface, and fluid replacement may be needed. As mentioned above, antimicrobial chemotherapy would employ beta-lactamase stable penicillins (e.g. nafcillin) against MSSA, whereas vancomycin, linezolid, quinopristin-dalfoprisin, or daptomycin would be used for MRSA.

Figure 26.4 Scalded skin syndrome results from infection of the skin with strains of Staphylococcus aureus producing a specific toxin, which destroys the intercellular connections in the skin, resulting in large areas of desquamation. The appearance may be confused with a burn.

(Courtesy of A. du Vivier.)

Toxic shock syndrome is caused by toxic shock syndrome toxin-producing Staph. aureus

This systemic infection came to prominence through its association with tampon use by healthy women, but it is not confined to women and can occur as a result of Staph. aureus infection at non-genital sites (e.g. a wound). Toxic shock syndrome (TSS) involves multiple organ systems and is characterized by fever, hypotension and a diffuse macular erythematous rash followed by desquamation of the skin, particularly on the soles and palms (Fig. 26.5). TSS is caused by exotoxins of Staph. aureus, most commonly TSST1, which behaves as a superantigen (stimulating T-cell proliferation and cytokine release; see Ch. 16). While the prevalence of TSS in the USA is currently estimated at <    200 cases/year, >    90% of adults carry antibodies to TSST1. Treatment of TSS includes steps to open the infected site (e.g. drainage), fluid replacement and antistaphylococcal chemotherapy.

Figure 26.5 Toxic shock syndrome results from systemic infection with Staphylococcus aureus, but has skin manifestations in the form of desquamation, particularly of the palm and soles.

(Courtesy of M.J. Wood.)

Streptococcal skin infections are caused by Strep. pyogenes (group A streptococci)

Streptococcal impetigo develops independently of streptococcal upper respiratory tract infection, and although up to 35% of patients carry the same strain in their nose or throat, colonization may well occur after the skin has become infected. The organisms are acquired through contact with other people with infected skin lesions and may first colonize and multiply on normal skin before invasion through minor breaks in the epithelium and the development of lesions. The various risk factors involved in the development of streptococcal impetigo are shown in Figure 26.6. Strep. pyogenes may also cause erysipelas, an acute deeper infection in the dermis. About 5% of patients with erysipelas go on to develop bacteraemia which carries a high mortality if untreated. As discussed previously, impetigo may also be caused by Staph. aureus and occasionally presents in more extreme bullous form (i.e. bullous impetigo) as blisters resembling localized scalded skin syndrome (see above).

Figure 26.6 Various factors are involved in the development of streptococcal skin infections. Particular M types of Streptococcus pyogenes have a predilection for skin, but various factors predispose the host (usually a child) to infection. Mixed infections with Staphylococcus aureus are also common.

Strep. pyogenes possesses certain surface proteins (M and T) which are antigenic. The species can be subdivided (typed) on the basis of these antigens, and it has been recognized that certain M and T types are associated with skin infection (and these differ from the types associated with sore throats). T proteins play no known role in virulence, and their function is unknown. M proteins are important virulence factors because they inhibit opsonization and confer on the bacterium resistance to phagocytosis. A variety of additional factors contribute to the virulence of the organism, such as lipoteichoic acid (LTA; a component of the Gram-positive cell wall) and F protein, which facilitate binding to epithelial cells.

Clinical features of streptococcal skin infections are typically acute

They develop within 24–48    h of skin invasion and trigger a marked inflammatory response as the host attempts to localize the infection (Fig. 26.7 and Fig. 26.8). Strep. pyogenes elaborates a number of toxic products and enzymes, such as hyaluronidase, which help the organism to spread in tissue. Lymphatic involvement is common, resulting in lymphadenitis and lymphangitis.

Figure 26.7 Impetigo is a condition limited to the epidermis, with typically yellow, crusted lesions. It is commonly caused by Streptococcus pyogenes either alone or together with Staphylococcus aureus.

(Courtesy of M.J. Wood.)

Figure 26.8 Erysipelas. Infection with Streptococcus pyogenes involves the dermal lymphatics and gives rise to a clearly demarcated area of erythema and induration. When the face is involved, there is often a typical ‘butterfly-wing’ rash, as shown here.

(Courtesy of M.J. Wood.)

Lysogenic strains of Strep. pyogenes produce pyrogenic exotoxins (SPE; formally called erythrogenic toxins). As with TSST1 in Staph. aureus (discussed previously), these toxins are superantigens with a potent influence on the immune system. The toxins (e.g. SPEA, B, and C) also act on skin blood vessels to cause the diffuse erythematous rash of scarlet fever, which may occur with streptococcal pharyngitis. Strep. pyogenes may also cause a form of toxic shock syndrome which has been especially associated with the production of the SPEA.

M protein is a major virulence factor in Strep. pyogenes with over 100 types, some of which (e.g. M49) are specifically associated with diseases such as acute glomerulonephritis

Acute glomerulonephritis (AGN) occurs more often after skin infections than after infections of the throat (see Ch. 18). It is characterized by the deposition of immune complexes on the basement membrane of the glomerulus but the precise role of the streptococcus in the causation is still unclear (see Ch. 17); 10–15% of individuals infected with a nephritogenic strain will develop AGN about 2–3    weeks after the primary infection. Most people recover completely, and recurrence after a subsequent streptococcal infection is rare. Rheumatic fever (see Ch. 18) very rarely follows skin infections with Strep. pyogenes.

Streptococcal skin infections are usually diagnosed clinically and treated with penicillin

Gram stains of pus from vesicles in impetigo show Gram-positive cocci, and culture reveals Strep. pyogenes sometimes mixed with Staph. aureus (Fig. 26.9). In erysipelas, skin cultures are often negative, although culture of fluid from the advancing edge of the lesion may be successful.

Figure 26.9 Gram-positive cocci in pus.

Penicillin is the drug of choice, although erythromycin, newer macrolides, or an oral cephalosporin may be used for penicillin-allergic patients. However, the prevalence of resistance (e.g. to erythromycin) in streptococci is increasing, and these drugs are not effective in mixed infections with Staph. aureus. Severe infections may require hospitalization.

Impetigo is prevented by improving the host factors associated with acquisition of the disease, as illustrated in Figure 26.6. Since AGN rarely recurs on subsequent streptococcal infection, long-term prophylaxis with penicillin is not indicated (in contrast to the long-term prophylaxis following rheumatic fever; see Ch. 18).

Cellulitis is an acute spreading infection of the skin that involves subcutaneous tissues

Cellulitis extends deeper than erysipelas and usually originates either from superficial skin lesions such as boils or ulcers or following trauma. It is rarely blood-borne, but conversely it may lead to bacterial invasion of the bloodstream. Infection develops within a few hours or days of trauma and quickly produces a hot red swollen lesion (Fig. 26.10). Regional lymph nodes are enlarged and the patient suffers malaise, chills and fever.

Figure 26.10 When the focus of infection is in the subdermal fat, cellulitis – a severe and rapidly progressive infection – is the typical presentation. Large blisters and scabs may also be present on the skin surface.

(Courtesy of M.J. Wood.)

The great majority of cases of cellulitis are caused by Strep. pyogenes and Staph. aureus. Occasionally, in patients who have had particular environmental exposure, other organisms may be implicated. For example, Erysipelothrix rhusiopathiae is associated with cellulitis in butchers and fishmongers, while Vibrio vulnificus and Vibrio alginolyticus may complicate traumatic wounds acquired in saltwater environments.

The pathogen causing cellulitis is isolated in only 25–35% of cases, and initial therapy should cover streptococci and staphylococci. Attempts can be made to confirm the clinical diagnosis by culture of:

Anaerobic cellulitis may develop in areas of traumatized or devitalized tissue

Such damaged tissue is associated with surgical or traumatic wounds or is found in ischaemic extremities. Diabetic patients are particularly prone to anaerobic cellulitis of their feet (Fig. 26.11). The causative organisms depend upon the circumstances of the trauma: infections in the lower parts of the body are most often caused by organisms from the faecal flora whereas wounds from human bites are infected with oral organisms. Foul-smelling discharge, marked swelling and gas in the tissues are characteristic of anaerobic cellulitis, and a mixture of organisms is usually cultured from the wound. Treatment needs to be aggressive to halt the spread of infection, and both antibiotics and surgical debridement are required. Osteomyelitis (see below) is a common sequela.

Figure 26.11 Severe progressive cellulitis of the foot. Such cellulitis is usually caused by anaerobic bacteria or a mixture of aerobes and anaerobes and is a particular problem in diabetic patients with peripheral vascular and neuropathic damage.

(Courtesy of J.D. Ward.)

Synergistic bacterial gangrene is a relentlessly destructive infection

This rare infection is caused by a mixture of organisms, typically microaerophilic streptococci and Staph. aureus. The gangrene most commonly follows surgery in the groin or genital area, starting at the site of a drain or suture. Cellulitis develops in the surrounding skin and extends rapidly (within hours), leaving a black necrotic centre. The condition is often fatal, and treatment requires radical excision of the necrotic area and systemic antibiotic therapy.

Necrotizing fasciitis is a frequently fatal mixed infection caused by anaerobes and facultative anaerobes

Although apparently resembling synergistic bacterial gangrene, necrotizing fasciitis is a much more acute and highly toxic infection, causing widespread necrosis and undermining of the surrounding tissues, such that the underlying destruction is more widespread than the skin lesion (Fig. 26.12). Necrotizing fasciitis has been most prominently linked by the popular media with Strep. pyogenes, where it has been frequently termed ‘flesh-eating bacteria’. However, the infection may be caused by a variety of other organisms, especially including MRSA. Patients with necrotizing fasciitis deteriorate rapidly and frequently die. Radical excision of all necrotic fascia is an essential part of therapy, along with antibiotics given both locally to the wound and systemically.

Figure 26.12 Necrotizing fasciitis of the abdominal wall. In patients such as this, infection can be seen rapidly spreading from its origin and causing deep and widespread necrosis. Complete debridement and intensive antimicrobial therapy is required, but the condition is often fatal.

(Courtesy of W.M. Rambo.)

Traumatic or surgical wounds can become infected with Clostridium species

Clostridium tetani gains access to the tissues through trauma to the skin, but the disease it produces is entirely due to the production of a powerful exotoxin (see Ch. 17).

Gas gangrene or clostridial myonecrosis can be caused by several species of clostridia, but Clostridium perfringens is the most common. The organism and its spores are found in the soil and in human and animal faeces, and can therefore gain access to traumatized tissues by contamination from these sources. Infection develops in areas of the body with poor blood supply (anaerobic), and the buttocks and perineum are common sites, particularly in patients with ischaemic vascular disease or peripheral arteriosclerosis. The organisms multiply in the subcutaneous tissues, producing gas and an anaerobic cellulitis, but a characteristic feature of clostridial infection is that the organisms invade deeper into the muscle, where they cause necrosis and produce bubbles of gas, which can be felt in the tissue and sometimes seen in the wound (Fig. 26.13). The infection proceeds very rapidly and causes acute pain. Much of the damage is due to the production by Cl. perfringens of a lecithinase (also known as alpha toxin), which hydrolyses the lipids in cell membranes, resulting in cell lysis and death (Fig. 26.14). The presence of dead and dying tissue further compromises the blood supply, and the organisms multiply and produce more toxin and more damage. Other extracellular enzymes may also play a role in helping the clostridia to spread. If the toxin escapes from the affected area and enters the bloodstream, there is massive haemolysis, renal failure and death.

Figure 26.13 Gas gangrene caused by Clostridium perfringens. Organisms from the fecal flora may contaminate a wound and grow and multiply in poorly perfused (anaerobic) tissue. Infection spreads rapidly, and gas can be felt in the tissue and seen on radiographs.

(Courtesy of J. Newman.)

Figure 26.14 The Nagler reaction. Clostridium perfringens produces alpha toxin, which is a lecithinase. If the organism is grown on a medium containing egg yolk (lecithin), enzyme activity can be detected as opacity around the line of growth (right). If anti-alpha toxin is applied to the surface of the plate before inoculation of the organism, the action of the toxin is inhibited (left). This test can be used to confirm the identity of a clostridial isolate.

Amputation may be necessary to prevent further spread of clostridial infection

Because of the rapid progression and fatal outcome of this type of clostridial infection, gangrenous areas require immediate surgery to excise all the affected tissue, and amputation may be necessary. Although some reports suggest that anti-alpha toxin may help if given early enough, antitoxin treatment is not generally viewed as effective, while treatment in a hyperbaric oxygen chamber, where available, may be helpful (i.e. oxygenation of tissue) in some cases.

Antibiotics (e.g. penicillin) are adjuncts to, not replacements for, surgical debridement.

Prevention of infection is of foremost importance. Wounds should be cleansed and debrided early to remove dead and poorly perfused tissue, which the anaerobes favour. Prophylactic antibiotics should be given preoperatively to patients having elective surgery of body sites liable to contamination with faecal flora (see Chs 33 and 36).

P. acnes go hand in hand with the hormonal changes of puberty which result in acne

An increased responsiveness to androgenic hormones leads to increased sebum production plus increased keratinization and desquamation in pilosebaceous ducts. Blockage of ducts turns them into sacs in which P. acnes and other members of the normal flora (e.g. micrococci, yeasts, staphylococci) multiply. P. acnes acts on sebum to form fatty acids and peptides which, together with enzymes and other substances released from bacteria and polymorphs, cause the inflammation (Fig. 26.15). Comedones are greasy plugs composed of a mixture of keratin, sebum and bacteria and capped by a layer of melanin (blackheads in popular terminology) (Fig. 26.16).

Figure 26.15 Typical lesions of acne. ‘blackheads’ are seen when plugs of keratin block the pilosebaceous duct.

(Courtesy of A. du Vivier.)

Figure 26.16 The proposed mechanism of the pathogenesis of acne. Hormonal changes in the host initiate the formation of comedones from normal follicles and thereby change the environment of Propionibacterium acnes and its physiologic properties. P. acnes is also known to be an immunostimulator.

Treatment of acne includes long-term administration of oral antibiotics

The antibiotics used to treat acne are usually one of the tetracyclines, or erythromycin. Other treatments include skin care, keratolytics and, in severe cases, synthetic vitamin A derivatives such as isotretinoin. Orally administered antibiotics reduce the surface numbers of P. acnes with a concomitant lowering of the free fatty acids, which act as skin irritants, which result from the activity of bacterial enzymes on sebum. Acne can be a problem for teenagers, but often disappears in older age groups as the sebaceous follicles become less active.

Other Gram-positive rods related to P. acnes, such as corynebacteria and brevibacteria, can also cause skin infections.

Leprosy is decreasing in incidence but still remains a concern

Leprosy has been recognized since biblical times, but in the past, the word was a generic term applied to several different diseases and also implying ‘moral uncleanliness’. Leprosy is thought to have spread to Europe in the sixth century, and by the thirteenth century there were some two hundred leper hospitals in England. Over the centuries that followed, leprosy declined in incidence, and by the fifteenth century was no longer endemic in England; in contrast tuberculosis was on the increase. Now leprosy is rare in the UK and USA and the WHO estimates that the number of new cases worldwide has decreased about 18% per year (2005–2009) with approximately 245 000 new cases detected in 2009. However, the disease still represents a significant problem in SE Asia, Africa and the Americas.

Leprosy is caused by Mycobacterium leprae

Mycobacterium leprae was discovered in 1873 by G.A. Hansen, who identified it as the first bacterial agent capable of causing human disease. Leprosy (Hansen’s disease) appears to be confined to humans. M. leprae is found in nine-banded armadillos, chimpanzees and mangabey monkeys; however, epidemiologic studies have not demonstrated a significant link between this carriage and human disease. Transmission of infection is directly related to overcrowding and poor hygiene and occurs by direct contact and aerosol inhalation. Relatively few organisms are shed from skin lesions, but nasal secretions of patients with lepromatous leprosy are laden with M. leprae. Arthropod vectors may play a role in transmission. Leprosy is not highly contagious, and prolonged exposure to an infected source is necessary; it seems that children living under the same roof as an open case of leprosy are most at risk. Ironically, because the lesions of leprosy are more obvious, patients were in the past excluded from the community and gathered in leper colonies, whereas tuberculosis is much more contagious, but people with tuberculosis were not shunned.

The clinical features of leprosy depend upon the cell-mediated immune response to M. leprae

M. leprae cannot be grown in artificial culture media, and little is known about its mechanism of pathogenicity. Two animal models have been used: infection in the armadillo and in the footpads of mice. The organism grows better at temperatures below 37°C, hence its concentration in the skin and superficial nerves, and it grows extremely slowly; in the mouse footpad the generation time is 11–13    days. Likewise in humans, the incubation period may be many years.

M. leprae grows intracellularly, typically within skin histiocytes and endothelial cells and the Schwann cells of peripheral nerves. The immune response is all important in deciding the type of disease.

M. leprae shares many pathobiologic features with M. tuberculosis, but the clinical manifestations of the diseases are quite different. After an incubation period of several years, the onset of leprosy is gradual and the spectrum of disease activity is very broad depending upon the presence or absence of a cell-mediated immune (CMI) response to M. leprae (Fig. 26.17). At one end of the spectrum is tuberculoid leprosy (TT), characterized by blotchy red lesions with anaesthetic areas on the face, trunk and extremities (Fig. 26.18). There is palpable thickening of the peripheral nerves because the organisms multiply in the nerve sheaths. The local anaesthesia renders the patient prone to repeated trauma and secondary bacterial infection. This disease state is equivalent to secondary tuberculosis (see Ch. 19), with a vigorous CMI response leading to phagocytic destruction of bacteria, and exaggerated allergic responses. TT carries a better prognosis than lepromatous leprosy (LL) and in some patients is self-limiting, but in others may progress across the spectrum towards LL.

Figure 26.17 Immunologic responses in leprosy. In tuberculoid leprosy (TT) the patient is capable of mounting an effective cell-mediated immune (CMI) response, which makes it possible for macrophages to destroy the organisms and contain the infection. At the other extreme, in lepromatous leprosy (LL) the patient is incapable of producing a CMI response and the organisms multiply unhindered. These patients have many acid-fast rods in their skin and nasal secretions, and are much more infectious than TT patients. Borderline lepromatous (BL), borderline borderline (BB), and borderline tuberculoid (BT) responses are found between these extremes.

Figure 26.18 Tuberculoid leprosy – a characteristic dry blotchy lesion on the face, but the diagnosis needs to be confirmed by microscopic examination of skin biopsy (see Fig. 26.21).

(Courtesy of the Institute of Dermatology.)

In LL, there is extensive skin involvement with large numbers of bacteria in affected areas. As the disease progresses there is loss of eyebrows, thickening and enlargement of the nostrils, ears and cheeks, resulting in the typical leonine (lion-like) facial appearance (Fig. 26.19). There is progressive destruction of the nasal septum, and the nasal mucosa is loaded with organisms (Fig. 26.20). This form of the disease is equivalent to miliary tuberculosis (see Ch. 19) with a weak CMI response and many extracellular organisms visible in the lesions. The gross deformities characteristic of late disease result primarily from infectious destruction of the nasomaxillary facial structures, and secondarily from pathologic changes in the peripheral nerves predisposing to repeated trauma of the hands and feet and subsequent superinfection with other organisms.

Figure 26.19 Extensive skin involvement in lepromatous leprosy results in a characteristic leonine appearance.

(Courtesy of D.A. Lewis.)

Figure 26.20 In lepromatous leprosy, the nasal mucosa is packed with Mycobacterium leprae, seen here in an acid-fast stain (Ziehl–Neelsen) of nasal scrapings.

(Courtesy of I. Farrell.)

Whether a patient develops TT or LL may in part be genetically determined. Patients with intermediate forms of the disease may progress to either extreme.

M. leprae are seen as acid-fast rods in nasal scrapings and lesion biopsies

Alertness to the possibility of leprosy when confronted with a patient with dermatologic, neurologic or multisystem complaints is of fundamental importance. Although the majority of cases are in people who are not native to Europe or the USA, the diagnosis should also be considered in those who have worked in endemic areas.

Nasal scrapings and biopsies of skin lesions should be stained by Ziehl–Neelsen or auramine stain to demonstrate acid-fast rods. In LL these are numerous, but in TT few if any organisms are seen, but the appearance of granulomas is sufficiently typical to allow the diagnosis to be made (Fig. 26.21). Remember that, in contrast to M. tuberculosis, the organism cannot be grown in vitro.

Figure 26.21 In tuberculoid leprosy, the organisms are much sparser but characteristic granulomas form in the dermis, as shown in this histologic preparation.

(Courtesy of C.J. Edwards.)

Leprosy is treated with dapsone given as part of a multidrug regimen to avoid resistance

If the disease is diagnosed early and treatment initiated promptly the patient has a much better prognosis. Dapsone (see Ch. 33) had long been the mainstay of therapy, but multidrug therapy is now used because of dapsone resistance:

Destruction of the organisms by effective antimicrobial therapy may result in an inflammatory response, erythema nodosum leprosum, which may be severe and, occasionally, fatal. Treatment with corticosteroids or thalidomide may be indicated.

Vaccination with bacille Calmette–Guérin (BCG) has been used in countries with high incidence where potential protection outweighs negative factors such as a positive skin test. Vaccination is not useful for immunocompromised individuals.

Mycobacterium marinum, M. ulcerans and M. tuberculosis also cause skin lesions

Mycobacterium marinum and M. ulcerans are two slow-growing mycobacterial species that prefer cooler temperatures and cause skin lesions. As its name suggests, M. marinum is associated with water and marine organisms. Human infections follow trauma, often minor such as a graze acquired while climbing out of a swimming pool or while cleaning out an aquarium, which becomes contaminated with mycobacteria from the wet environment. After an incubation period of 2–8    weeks, initial lesions appear as small papules, which enlarge and suppurate and may ulcerate. Histologically, the lesions are granulomas and hence the name ‘swimming pool granuloma’ or ‘fish-tank granuloma’ (Fig. 26.22). Sometimes the nodules follow the course of the draining lymphatic and produce an appearance that may be mistaken for sporotrichosis (see below).

Figure 26.22 Fish-tank granuloma caused by Mycobacterium marinum infection of a lesion acquired while cleaning out a fish tank.

(Courtesy of M.J. Wood.)

M. ulcerans causes chronic, relatively painless cutaneous ulcers known as ‘Buruli ulcers’. This disease is prevalent in Africa and Australia, but is rarely seen elsewhere.

Tuberculosis of the skin is exceedingly uncommon. Infection can occur by direct implantation of M. tuberculosis during trauma to the skin (lupus vulgaris) or may extend to the skin from an infected lymph node (scrofuloderma).

M. furfur is the cause of pityriasis or tinea versicolor

The yeast M. (Pityrosporum) furfur is a common skin inhabitant. The change from commensalism to pathogenicity appears to be associated with the phase change from yeast to hyphal forms of the fungus, but the stimulus for this is unknown. Infections are usually confined to the trunk or proximal parts of the limbs and are associated with hypo- or hyperpigmented macules that coalesce to form scaling plaques. The lesions are not usually itchy and in some patients, they resolve spontaneously.

Malassezia yeasts are also thought to be involved in the pathogenesis of seborrhoeic dermatitis and dandruff.

Diagnosis of pityriasis versicolor can be confirmed by direct microscopy of scrapings

Direct microscopy of scrapings shows characteristic round yeast forms (Fig. 26.23), and treatment with a topical azole antifungal (see below) or with selenium sulphide (2.5%) lotion is appropriate.

Figure 26.23 Infected skin scales stained to show the thick-walled yeast forms of Malassezia furfur and the short angular hyphae.

(Courtesy of Y. Clayton and G. Midgley.)

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