Pathogenesis of dermatophytes

Dermatophyte infections involve three main steps:

1- adherence to keratinocytes,
2- penetration through and between cells,
3- development of a host response.

1) ADHERENCE
• Superficial fungi must overcome several obstacles in order for the arthroconidia (the infectious element) to
adhere to keratinized tissue. They must resist :
1- the effects of ultraviolet light,
2- variation in temperature and moisture,
3- competition from normal flora, and
4- sphingosines produced by keratinocytes.

N.B. Fatty acids produced by sebaceous glands are fungistatic Their presence in postpubertal children may
account for the dramatic decrease in tinea capitis infections after puberty.

2) PENETRATION
• After adherence, spores must germinate and penetrate the stratum corneum at a rate faster
fas than
desquamation Penetration is accomplished by the secretion of proteinases, lipases,
lipases and mucinolytic
enzymes, which also provide nutrients to the fungi.
fun
• Trauma &maceration
maceration also facilitate penetration and are important factors in the pathogenesis of tinea pedis.
• Fungal mannans in the cell wall of dermatophytes may also decrease the rate of keratinocyte proliferation.
New defenses emerge once the deeper
deepe layers of epidermis are reached, including:
- competition for iron by unsaturated transferrin and
- inhibition of fungal growth by progesterone.

3) DEVELOPMENT OF A HOST RESPONSE

• Immune detection and chemotaxis of inflammatory cells may occur through several mechanisms :
- Some fungi produce low-molec
molecular-weight chemotactic factors.
- Others activate complement via the alternative pathway, creating complement-derived
complement chemotactic factors.

• Type IV, or delayed-type

type hypersensitivity (DTH), plays a major role in combating
ating dermatophytoses.
This arm of cellular immunity is maintained by interferon-γ
interferon γ secre-on from type 1 T-helper
T lymphocytes.

• In patients without previous exposure to a dermatophyte :

- primary infection causes minimal inflammation, and a trichophytin skin
skin test is negative.
- The infection produces mild erythema and scale,, the result of increased keratinocyte turnover.

- It is hypothesized that dermatophyte antigen is then processed by epidermal Langerhans cells and
presented in local lymph nodes to T lymphocytes.
lymphocytes. The T lymphocytes undergo clonal proliferation and
migrate to the infected site to attack the fungus.
- Soon, the fungus is cleared, and the lesion spontaneously resolves.

• The trichophytin skin test is now positive, and clearing of a second infection will be more rapid.

- Unlike the primary lesion, these are KOH examination

examination and culture negative.
- These
hese reactions may take the form of follicular papules, erythema nodosum, vesicular id of the hands
ha
and feet, erysipelas-like,
like, erythema annulare centrifugum, or ur-caria (see Chap. 17).
Although the precise mechanism is unknown, these reactions are associated with a DTH response to
the trichophytin test and may involve a local DTH response to systemically
systemically absorbed fungal antigen.