’111
`
`II IIIII II
`
`IIII
`
`II ’111 IIII I II1%11111111’11¸
`
`Dermatology ! 997; 194(suppl 1 ):32-36
`
`R. C. Summerbell
`
`Mycology, Ontario Minist~T of Health,
`Etobicoke, Ont., Canada
`
`Epidemiology and Ecology of
`Onychomycosis
`
`Key Words
`Trichoph),ton
`Dermatophytes
`Onychomycosis
`hmnunocompromised patients
`Age~related susceptibility
`Transmission
`Candida
`Non-dermatophytes
`
`Abstract
`The epidemiology and ecology of onychomycosis am complex and little under-
`stood, Most is known about tinea unguium, demmtophytic nail infection, and its
`causative agents. This is often categorised according to the precise locus on the
`nail of the infection. The principal infectious propagules are thought to be the
`arthroconidia or chlamydospores which form within the solid substratum of in-
`vaded nail tissue, The process of infecting new hosts api~ars to be facilitated by
`abrasion, moistening and scratching. The rote of the non-dermatophyte yeast
`Candida as an agent of onychomycosis per se may have been overestimated,
`The range of interactions between dermatophytes and non-dennatophytes in
`nails is complex and poorly undm:stood. There may be at least six distinct eco-
`logical categories of non-dermatophyte isolations from nails. It would be of clin-
`ical interest m know which species found in mixed infections were never able
`to advance beyond ’secondary colonisation’, as they would not require specific
`treatment.
`
`The epidemiology and ecology of onychomycosis am
`surprisingly complex. A number of timtors, each simple on
`its own, come together in this area to form a composite of
`overlapping probabilities that few understand well. More-
`over, the biology of many organisms in nails is poorly
`known, and theoretically simple methods of clarit~,ing such
`matters are difficult to co-ordinate with clinical realities.
`The best-known aspect of onychomycotic epidemiology
`is that related to tinea unguium, dennatophytic nail infec-
`tion, and its causative agents. Less well understood is the
`epidemiology of non-dermatophytes causing nail infections
`of various kinds. Least welt known, and often a matter for
`free speculative contention, is the interaction between der-
`matophytes and non-dermatophytes in nails. These subjects
`will be addressed in order below:
`
`Dermatophytes as Sole Agents of Tinea unguium
`
`Of the more than 20 dennalophyte species that regularly
`cause human infections, only a t~w am significant agents of
`onychomycosis. The ability to cause this disease is evi-
`dently specialised, since [here is no known parallel disease
`affecting kemtinous claws or hooves of our non-anthropoid
`mammalian relatives. Dermatophyte species or variants
`competent at causing tinea ungnium are obligate human
`pathogens which have lost the ancestral heterothallic sexu-
`ality of the dennatophyte group and which, in the 2 most
`common species, often show degenerate asexual reproduc-
`tion. with conklia reduced in number or simplified or dis-
`torted in form. They exhibit a great deal uf variability in
`colony coloration and microscopic morphology, suggestive
`
`KAR.G ER
`
`EMail ka~gcr(~i)kargcr, ch
`Fax+41 61 30(~ 12 34
`
`’i’hi:~ a~licle is also a¢¢exsibl¢ o~ti~e a~:
`h=g~://r.!ioMedNe~.com/karger
`
`Richard C, Summel’~’~elL PhD
`Mycology, Ontario MinislU of ttealth
`81 Resou~’es Road, Eloblcoke, Out, M9P 3TI {Canada)
`"I?1. +1 4~6 235 5719, Fax +! 4~(~, 235 5951
`E~MaI~ su mmerdr(i~ epo gov, on.ca
`
`."5
`g
`
`i5~a
`
`ARGENTUM EX1031
`
`Page 1
`
`

`

`abundance, may merely signify pockets of sapmbic colo-
`nisation in nails split or fissured by an urn’elated disease
`process (e.g. dermatophytosis, psoriasis) so that micro-
`scopic humid chambers suitable for yeast proliferation have
`been produced, Non-C.-albicans Camlida species of the
`normal skin flora may often be isolated in similar circum-
`stances and may persist over time in these harmless coloni-
`sations. Distinction of these co/onisations from genuine
`cases of infection by these fungi (especially Candida para-
`psilosis) can best be accomplished by showing microscopi-
`cally that some pseudomycelial tissue penetration has been
`accomplished in the purported infection. (If tree mycelia
`are seen, the possibility of overgrown or senescent derma-
`tophyte material should be stron,,ly~ considered - see be-
`low,)
`Approximately 35 non-dermatophyte filmnentous funsal
`species have been shown to be capable of causing or sus-
`taining onychomycosis as sole aetiologicat agents. In addi-
`tion, numerous other species have been alleged but not well
`demonstrated to do so, Most virulent among the well-estab-
`lished agents are ScytatMium dimidiamm (synanamorph
`N(ItIF(L~5"i(1 mangiJ~,~zte, formerly tlende~;s’omda toruloidea)
`and S. hyatimm~, which appear to be as effective as der-
`matophytes in infecting heavily keratinised epidem~is and
`nails [9]. These fungi have somewhat distinctive filaments
`in nai! tissue and are rarely or never isolated as contami-
`nants in temperate areas of the world; thus, isolation usually
`signifies infection, and this can readily be confirmed by
`direct microscopy. Most dermatomycotic agents, however,
`are common contaminants associated with feet and nails
`and only occasionally "cross over’ into aetiologicat status,
`The evems precipitating such a mmsition are unknown but
`may include attenuation of host defences in age (especially
`in the ekterly), nai! injury and prior nail infection by a der-
`matophyte. When, in any case, they are present in nails as
`sole agents of infection, they may have distinctive elements
`produced in or from host tissue (e.g. unusual filaments,
`conidiophoms, conidia), in which case in~ection is easy to
`confirm, or only indistinctive hyphae in tissue, in which
`case sole infection may be difficult to confirm except by
`repeated sampling (see below). Such difficuh-to-conflrm
`infections may be seen with selected members of the gen-
`era Scopulariol)sis, Fusarium, A,q)e~igillus and AtWrnaria,
`as well as with less common fungi.
`
`Complex Relations between Dermatophytes and
`Non-Dermatophytes, Including Mixed Infections
`
`In an active bacterial infection, it would be almost un-
`thinkable to have entire areas of the affected tissue invested
`only with dead bacterial cells and no living inoculum. Fila-
`mentous funsal colonies, however, are continuous, modular
`bodies which, like trees with dead limbs, can be seen in the
`space they occupy either as living or dead forms. The study
`of onychomycosis is primm’ily rendered complex by the
`fact that approximately 20% of al! samples from nails in-
`vested with dermatophyte filaments happen m include ma-
`terial only from the ’dead branches’, or senescent growth
`fronts, of the somewhere still active dermatophyte colony;
`(This type of sample yields a negative culture, often mis-
`leadingly referred to as ’false-negative’ even though the
`culturing technique reflects the condition of the sample ma-
`terial with impeccable accuracy.) When these dead der-
`matophyte filaments, seen in direct microscopy, coincide
`with cultures positive for a fungus growing t¥om contami-
`nating spores or conidia, this is easily misinterpreted as sig-
`nifying a non-dermatophyte infection, especially if the con-
`taminating inoculum is of a species well known to cause
`occasional onychomycosis. Similarly, when these dead der-
`matophyte elements are intermingled with living elements
`of a co-infecting non-dennatophyte, the diagnosis of a pure
`non-dermatophyte infection may be incorrectly made. Con-
`versely, the diagnostician may err oppositely when con-
`fronted with a genuine non-dermatophyte infection by mis-
`interpreting the non-dennatophyte filaments in the nail as
`dead dermatophyte filaments, and misattributing the non-
`dennatophyte culture to contamination. A non-dermato-
`phyte genuinely participating in a mixed infection may sim-
`ilarly be misinterpreted as a contaminant if a dermatophyte
`grows.
`The degree of overlap among these and related possibil-
`ities effectively precludes a firm diagnosis of non-dermato-
`phytic or mixed onychomycosis from any single specimen
`where: (a) a non-dermatophyte known to cause onychomy-
`cosis occasionally is isolated in the presence or absence of
`a dermatophyte and (b) the elements seen in direct mi-
`croscopy are generic funsal filaments and do not unequivo-
`cally confirm or exclude the non-dermatophyte in question.
`The non-dermatophyte in such cases is an organism only
`tentatively associated with disease, a situation best clarified
`using Koch’s first postulate of pathogenicity, namely, con-
`sistency of association of the putative aetiological agent
`with the disease [10f This consistency is demonstrated by
`examining one or more successive repeat samples from the
`patient’s lesion and finding the same non-dermatophyte
`
`34
`
`Dermatology 1997:19~t(s~pp! I);32~-3~i
`
`Summerbell
`
`g
`
`g~
`
`Page 2
`
`

`

`References
`
`I Tanaka S, Summerbeli RC.’lM~boi R, Kaaman
`"1\ Sohnte PG, Matsumoto "L Ray TL: Ad-
`vm~ees in dermatophytes filial non-dermato-
`phytosis. J Med Vet Mycol i992:30(suppl 1):
`29-:39.
`2 ZaiasN: Onyehomycosis. Arch lX’.rmato11972:.
`t 05:263-274.
`3 Da~liel CR IlL Nortor~ LA, Seher RK: "171e
`spectrum of nai! disease in patients with human
`immum×teficiency vires infection. J Am Acad
`Dennalol 1992:27:93-97.
`4 IleikkWa It. Stubb S: The prevalence or ony-
`chomycosis i~ Nnland. Br J Dcrmaml 1995;
`t 33:69%G03.
`
`5 English MR Atkinson R: Onychomycosis in
`elderly chiropody patients, gr J 1)emmtot 1973:
`9 t :67,,,,92.
`6 A|jabrc SH. Richardson MD, Scott EM,
`Rashid A: Adhem~ce <ff arlhroco~fidia and
`germlings of anthropophilic varieties of 7)q-
`chophytot,~ menragrophytes to human cortleo-
`cytes as an early event in tl~e pathogenesis of
`demnatophytosis, Ctin Exp Dermatol 1993;t 8:
`231-.--235,
`7 Weitzman L Summertx, ll RC: The dermam-
`phytes. Clin Microbiol Rev 1995;8:24%.-259,
`8 .Zaias N. qk~sfi A. Rebeli G, Morel|i R. Ba~xlazzi
`F. el al: Autosomal dominant pattern of distal
`subungua[ onychonlycosis caused by 2)’icho-
`phy¢on rubrum. J Am Acad Dermatol 1996:
`34:302--304.
`
`9 MooreMK:th’tMelwotudalorufoideaand&3"~
`talidium hyalitmm infections in London. En-
`gland.J Med Vet Myeol 1986;24:219-o230.
`I 0 Stillcr MJ. Rosenthal RC, Smnmerbe[1 J, et al:
`Owehomycosis of t!~e ~renails caused by
`(TtaetomOtm globosum. J Atlt Acad Dermatot
`1992:26:775--.,776,
`I 1 Waishe MM, English MP: Fungi in nails. 13rJ
`l)cmaatol 1966:78:198-,207.
`i2 Summerbeli RC, Kane J, Kmjden S: Ony-
`chomycosis, tinea pedis and tinea raanuunt
`caused by non-demmtophytic liiame~tous fun-
`gi, Mycoses t989:32:609-612,
`
`36
`
`Dem~au~log} ~997;194(suppl 1}:32---36
`
`Summerbell
`
`Page 3
`
`