Bullous impetigo is a bacterial skin infection caused by ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

'' that results in the formation of large blisters called bullae, usually in areas with skin folds like the armpit, groin, between the fingers or toes, beneath the breast, and between the buttocks. It accounts for 30% of cases of

impetigo Impetigo is a bacterial infection that involves the superficial skin. The most common presentation is yellowish crusts on the face, arms, or legs. Less commonly there may be large blisters which affect the groin or armpits. The lesions may be pa ...

, the other 70% being non-bullous impetigo. The bullae are caused by exfoliative toxins produced by ''Staphylococcus aureus'' that cause the connections between cells in the uppermost layer of the skin to fall apart. Bullous impetigo in newborns, children, or adults who are immunocompromised and/or are experiencing

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, can develop into a more severe and generalized form called

staphylococcal scalded skin syndrome Staphylococcal scalded skin syndrome (SSSS) is a dermatological condition caused by ''Staphylococcus aureus''. Signs and symptoms The disease presents with the widespread formation of fluid-filled blisters that are thin walled and easily ruptured ...

(SSSS). The mortality rate is less than 3% for infected children, but up to 60% in adults.Yasushi, Hanakawa. "Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome." ''Journal of Clinical Investigation''. 110.1 (2002): 53-60.

Signs and symptoms

Bullous impetigo can appear around the diaper region,

axilla The axilla (also, armpit, underarm or oxter) is the area on the human body directly under the shoulder joint. It includes the axillary space, an anatomical space within the shoulder girdle between the arm and the thoracic cage, bounded superior ...

, or neck. The bacteria causes a toxin to be produced that reduces cell-to-cell stickiness (adhesion), causing for the top layer of skin (epidermis), and lower layer of skin (dermis) to separate. Vesicles rapidly enlarge and form the bullae which is a blister more than 5mm across. Bullae is also known as

. Other associated symptoms are itching, swelling of nearby glands, fever and diarrhea. Pain is very rare. Long-term effects: once the scabs on the bullous have fallen off, scarring is minimal. Possible long-term effects are kidney disease.

Cause

Exposure is most commonly seen in hospital wards and nurseries, and can be passed from person to person in other settings, such as close contact sports. Therefore, the patient is advised to try to limit human contact as much as possible to minimize the risk of spreading the infection.

Infectious period

After 48 hours the disease is considered no longer contagious assuming the proper antibiotic treatments have been administered.

Pathogenesis

Exfoliating toxins are serine proteases that specifically bind to and cleave

desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disea ...

1 (Dsg1). Previous studies suggested that exfoliating toxins bind to

gangliosides A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. N-acetylneuraminic acid, ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative ...

, causing a release of protease by keratinocytes acting as

superantigens Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are p ...

in stimulating the skin's immune system. A more recent proposal states there are three known exfoliating toxins; ETA, ETB, and ETD which act as a glutamic acid-specific serine protease with concentrated specificity. Which results in the cleavage of human Dsg1 at a unique site after glutamic acid residues causing deactivation. Proteolysis of the peptide bond leading up to the dysfunction of Dsg1 and the desmosome allows for an understanding as to why the bullous forms, making the peptide bond crucial for proper function if Dsg1.

''S. aureus''

A phyogenic non-motile Gram-positive cocci which forms into grape like clusters. Just like other forms of staph, ''S. aureus'' has a variety of virulence factors which include surface proteins involved in adherence, secretion of enzymes that degrade proteins, and secrete toxins which damage the host's cells. ''S. aureus'' expresses surface receptors for

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

, and

vitronectin Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene. Vitronectin binds to integrin alpha-V beta-3 and thus promotes c ...

. These surface receptors allow a bridge to be formed which binds to host endothelial cells. Lipases allow for the degradation of lipids on the skin surface and its expression can be directly correlated with its ability of the bacteria to produce abscesses.Kumar, V, A Abbas, and N Fausto. "Pathologic Basis of Disease." 7th. Chicago: Robbins and Cotran, 2004. 620

Diagnosis

Observing the skin's physical appearance, or swabbing a culture of the lesion for S. ''aureus''. Nasal swabs from the patient's immediate family members are necessary to identify them as being asymptomatic nasal carriers of S. ''aureus''.

Histology

The epidermis is composed of four layers,

stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...

stratum spinosum The stratum spinosum (or spinous layer/prickle cell layer) is a layer of the epidermis found between the stratum granulosum and stratum basale. This layer is composed of polyhedral keratinocytes. These are joined with desmosomes. Their spiny (Latin ...

stratum granulosum The stratum granulosum (or granular layer) is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum (stratum lucidum on the soles and palms).James, William; Berger, Timothy; Elston, Dirk (2005) ''A ...

, and

stratum corneum The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compact ...

.Roy, S. (2009). Histology of the normal skin. Retrieved from http://www.histopathology-india.net/NH.htm The cleavage plane can be found either subcorneally or within the upper stratum granulosum. The roof of the pustule is parakeratotic stratum corneum, and the floor is formed of keratinocytes, which may or may not be acantholytic.Carter, D, J Greenson, H Oberman, V Reuter, and StolerM. "Sternberg's Diagnostic Surgical Pathology." 4th. 1. New York City: Lippincott Williams & Wilkins, 2004. 17f Neutrophils begin to fill the pustule. Toxins are produced by S. ''aureus'' and target desmoglein, which is a desmosomal cell-cell adhesion molecule found in the upper levels of the epidermis. This correlates with the subcorneal localization of the bullae.

Uncommon variants

Erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...

Systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

Pemphigus vulgaris Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word ''pemphix'', meaning blister. It is classified as a type II hypersensitivity reaction in which antibodies ...

Differential

HPV Human papillomavirus infection (HPV infection) is caused by a DNA virus from the '' Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and re ...

* Insect bites * Burns * Herpes simplex 1/2

Prevention

Since the common pathogens involved with impetigo are bacteria naturally found on the skin, most prevention (especially in children), is targeted towards appropriate hygiene, wound cleaning, and minimizing scratching (i.e. by keeping nails trimmed and short). Avoiding close contact and sharing of items such as towels with potentially infected individuals is also recommended.

Management

Antibiotic creams are the preferred treatment for mild cases of impetigo, despite their limited systemic absorption. Such prescribed ointments include neosporin, fusidic acid,

chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, a ...

and

mupirocin Mupirocin, sold under the brand name Bactroban among others, is a topical antibiotic useful against superficial skin infections such as impetigo or folliculitis. It may also be used to get rid of methicillin-resistant ''S. aureus'' (MRSA) wh ...

. More severe cases of impetigo however (especially bullous impetigo) will likely require oral agents with better systemic

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

, such as

cephalexin Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a beta-lactam antibio ...

. Cases that do not resolve with initial antibiotic therapy or require hospitalization may also be indicative an MRSA infection, which would require consultation with a local microbiologist. Antibiotic treatment typically last 7–10 days, and although highly effective some cases of methicillin resistant S. aureus (MRSA) may require longer therapy depending on the severity of infection and how much it has spread.

References

External links

{{DEFAULTSORT:Bullous Impetigo Bacterium-related cutaneous conditions