Indian J Dermatol. 2011 May-Jun; 56(3): 259261.

doi: 10.4103/0019-5154.82476
PMCID: PMC3132899
PATHOGENESIS OF DERMATOPHYTOSES
Ram Tainwala and YK Sharma
From the Department of Dermatology, Dr. D. Y. Patil Medical College, Pimpri, Pune, India.
Address for correspondence: Dr. Ram Tainwala, 1001, Swapna-lok tower-1, Marve Road, Malad-west, Mumbai 64, India. E-mail:
drtainwala@gmail.com
Received August 2010; Accepted October 2010.
Copyright Indian Journal of Dermatology
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported,
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Abstract
Dermatophytes can survive solely on outer cornified layers of the skin. The ability of certain fungi to
adhere to particular host arises from numerous mechanisms and host factors, including the ability to
adapt to the human body. Natural infection is acquired by the deposition of viable arthrospores or
hyphae on the surface of the susceptible individual. After the inoculation in the host skin, suitable
conditions favor the infection to progress through the stages of adherence and penetration.
Development of host response is mostly by a T-cell mediated response of delayed-type hypersensitivity.
Antibody formation does not seem to be protective. Natural defenses against dermatophytes depend on
both immunological and nonimmunological mechanisms.
Keywords: Dermatophytoses, pathogenesis, tinea
Introduction
Dermatophytes can survive solely on outer cornified layers of the skin.[1,2] The ability of certain fungi to
adhere to particular host arises from numerous mechanisms and host factors, including the ability to
adapt to the human body.[1] Natural infection is acquired by the deposition of viable arthrospores or
hyphae on the surface of the susceptible individual.[3] After the inoculation in the host skin, suitable
conditions favor the infection to progress through the following stages.[4]
Adherence
After overcoming obstacles (ultraviolet light, temperature, and moisture variation) and competing with
the normal flora and sphingosines produced by keratinocytes and the fatty acids produced by the
sebaceous glands, the arthroconidia (infectious element) adhere to the keratinized tissue.[4] The
germination of arthroconidia and hyphal growth adherence proceeds radially in multiple directions.
[5,6] Little is known about the factors that mediate adherence of dermatophytes; however, it has been
hypothesised that dermatophytic-secreted proteases could facilitate or even be necessary for efficient
adherence. The ability of Trichophyton rubrum to adhere to epithelial cells has been attributed to
carbohydrate-specific adhesins, expressed on the surface of microconidia. From a morphological point
of view, fibrillar projections have been observed in T. mentagrophytes during the adherence phase. At
the skin surface, long and sparse fibrils connect fungal arthroconidia to keratinocytes and to each other,
while in the inner skin layers, newly formed arthroconidia show thin and short appendices covering
their entire surface; the latter begin to vanish as a large contact area is established between conidia and
skin tissue.[5]
Development of host response
Acquired resistance
Antibodies
Penetration
Dermatophytes are provided with an arsenal of proteases aimed at the digestion of the keratin network
into assimilable oligopeptides or amino acids.[5] Once established, the spores must germinate and
penetrate the stratum corneum at a rate faster than desquamation. Penetration is accompanied by
dermatophytes secreting multiple serine-subtilisins and metallo-endoproteases (fungalysins) formerly
called keratinases that are found almost exclusively in the dermatophytes.[5,7] A direct relationship
between keratinases and pathogenicity was established by Viani et al. However, little information is
available about hydrolases, such as lipases, and a ceramidase, produced by these fungi.[5] The
mechanism by which mucolytic enzymes, which help in penetration, also provide nutrition to the fungi
is unknown.[4,5,8] These dermatophytic keratinolytic proteases cannot act before disulfide bridges are
reduced within the compact protein network constituting keratinized tissues. This was recently shown to
depend from a sulfite efflux pump encoded by the Ssu1 gene. Sulfite excretion by this transporter allows
sulfitolysis of proteins, rendering them accessible for proteases, and functions in the same time as a
possible detoxification pathway, a future target for new anti-fungal treatments.[5] The protease
production in T. rubrum is highly host specific showing reduced physiological activity when growing on
their preferred host[9,10] (Rippon,1988; Rippon and McGinnis,1995). This would explain the well-
established anthropophization of these species. Ranganathan reported a similar finding on the
relationship between chronicity and low-protease profile of T. rubrum isolates.[11] Fungal mannans in
the dermatophyte cell wall have immuno-inhibitory effects and T. rubrum cell wall mannans (TRM)
seem to be involved in an immunosuppression phenomenon, inhibiting lymphoproliferative response of
mononuclear leukocytes in response to several antigens (dermatophytic or not) and mitogens. Although
specific suppressor T cells are eventually activated during persistent infections, target cells for TRM
action appear to be monocytes rather than lymphocytes. Trichophyton rubrum mannans may also
decrease the keratinocyte proliferation rate, directly or via lymphocyte function alteration, contributing
significantly to the chronicity of T. rubrum infection.[4,5,7,12] However, clinical heterogenicity in
substrate preference, with all dermatophyte species invading the stratum corneum of the skin but wide
variation in their capacity to invade hair and nail, has been seen.[13]
Fungal metabolic products diffuse through the malphigian layer to cause
erythema, vesicle or even pustule formation along with pruritus. Their in vivo activity is restricted to the
zone of differentiation, newly differentiated keratin and Adamson's fringe within the hair shaft.[12]
Acute dermatophytosis is associated with a DTH skin response against them, while persistent disease
corresponds to IH responses, to high levels of IgE and IgG4 antibodies, and to the production of Th2
cytokines by mononuclear leukocytes.[5]
The efficient and protective response against dermatophytosis is a cell-mediated
response of the DTH, characterized namely by the action of macrophages as effector cells, interferon-!
secretion from type 1 T-helper lymphocytes and by some key cytokines like interferon-" (IFN-").
Immune detection and chemotaxis occur via low-molecular weight chemotactic factors or alternative
complement pathway activation. However, the immune response that is raised, and especially the
degree of inflammation, varies according to the dermatophyte species, the host species and the
pathophysiological status of the host.[4,5,14] In general, the zoophilic species cause more inflammatory
infections, which may heal spontaneously and result in relative resistance to re-infection. The
anthropophilic species usually cause more chronic, less circumscribed infections, which result in less
resistance to re-infection.[15] Primary infection produces negative trichophytin test and minimal
inflammation (mild erythema and scaling) due to increased keratinocyte turnover.
Antibody formation does not seem to be protective.[16] The dermatophyte antigen is thought
to be processed by epidermal Langerhans cells and presented in local lymph nodes to T lymphocytes
which proliferate, migrate to the infected site, and produce inflammation. The epidermal barrier
becomes permeable to transferring and migrating cells leading to spontaneous resolution of lesions.
Trichophytin skin test is now positive and clearing of second infection will be more rapid.[4] Rivalier
showed that a dermatophytic infection in humans results in a relative resistance to subsequent infection
called le phenomene de la reaction acceleree or le phenomene de Bruno Bloch,[17] mainly by the
Hypersensitivity (Trichophytin reaction)
Nonspecific resistance
Invasive dermatophytosis
inflammatory forms (kerion), caused by zoophilic species, but not always follow the more chronic
anthropophilic infections.[15,18] Barlow and Chattaway[18] pointed out that fungi which do not invade
the hair follicle do not seem to give rise to an equivalent immunity when growing in the horny layer of
the smooth skin. In contrast, Desai et al. could not demonstrate such acquired immunity in
experimental T. rubrum infection of smooth skin.[15,19]
Dermatophytid reactions (45% of patients) are inflammatory
eczematous allergic skin reactions at sites distant from primary fungal infection.[15] Being KOH and
culture negative, it is associated with a DTH response to trichophytin test and may involve a local DTH
response to systemically absorbed fungal antigen.[15,20]
Natural defenses against dermatophytes depend on immunological and
nonimmunological mechanisms.[21] Several host factors like number and activity of sebaceous glands
(due to inhibitory effect of sebum on dermatophytes) in a particular body region, breaks in the skin
barrier, increased hydration and macerated skin can encourage dermatophyte invasion.[1]
Host factors that help limiting the infection to keratinized tissue include their preference for cooler skin
temperatures than the normal body temperature, serum inhibitory factors (beta-globulins, ferritin and
other metal chelators) binding to iron essential for growth of dermatophytes.[1,7,22,23] Unsaturated
transferrin inhibits the growth of dermatophytes by binding to the hyphae.[24] A growth modifying, !
macroglobulin keratin inhibitor, has also been identified in serum.[25] The natural resistance of scalp to
T. capitis in adults may be due to post pubertal, fungistatic and fungicidal, long chain saturated fatty
acids.[26]
Commensal Pityrosporum yeast aids lipolysis and increases pool of fatty acids available for inhibiting
fungi.[22] Humoral immunity has a minor role in acquired resistance to dermatophytoses.[15,27]
Invasion or dissemination of dermatophytes within the dermis is rare, but
occurs mostly in the setting of a chronic dermatophyte infection (mostly T. rubrum) in an
immunosuppressed individual. Acute onset of ulcerating or draining dermal and subcutaneous nodes
occurs after hematogenous spread. A more indolent process can occur, presenting most often as tender
nodules over extremities.[2830]
A rare case of a fatal dermatophytic disease due to T. Schnleini is also documented in a family of three
siblings with a familial immunological defect after eight years of evolution (Hadida et Schousboe).[31]
Footnotes
Source of Support: Nil
Conflict of Interest: Nil.
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