MYCOTIC DISEASES

Dr. Mahmoud Farghali

mahmoud.farghali@pharm.tanta.edu.eg
 C- COLONIZATION AND RESULTANT DISEASES
In general, humans have a high level of natural immunity to fungi. These include; intact skin
and mucosal surfaces serve as barriers to any infection. Fatty acid content, pH, epithelial
turnover, and the normal bacterial flora of the skin appear to contribute to host resistance.
Humeral factors such as transferrin have been shown to restrict the growth of fungi may be by
limiting the amount of available iron.
Thus, most fungal infections are mild and self-limiting. Fungal colonization is capable of
causing the following five types diseases:

I - Superficial mycoses:
Infections of outermost layers of skin and hair it is one of the cosmetic problems. Four types of
these infections are known .
1- Pityriasis versicolor:
The etiological agent is Malassezia furfur (Pityrosporum orbiculare), a yeast like normal flora. It
is found in areas of the body rich in sebaceous glands. It causes lesions commonly on the upper
torso, arms, neck and abdomen as hyper-of hypo pigmented macular lesions. They scale
very easily giving the affected area a dry, chalky appearance.
Diagnosis :
Clinical symptoms.
Direct microscopic examination in a mount of 10% .KOH. Both oval (young cells) and hyphal form
(upon aging) are detected, i.e. dimorphic.

https://www.nhs.uk/conditions/pityriasis-
versicolor/#:~:text=Check%20if%20you%20have%20pityriasis%20versicolor&text=On%20white%20skin%2C%20the%20patches,upper%20arms%2C%20
neck%20or%20tummy.
 2- Tinea nigra:
The etiological agent is Hortaea werneckii , a common saprophytic fungus occurs in soil,
compost, humus of sewage and on wood in humid tropical and sub-tropical regions.
Familial spread of infection has also been reported. It is yeast-like fungi that produce melanin
giving brown to black color to the organism.
Who is infected? Tinea nigra appears to occur less often in the black population than in others.
Any age may be affected and more common in young people with fair skin aged 3-28 years
who visited beaches and in females than males (3:1).
Clinical manifestations appear as light brown to black discoloration macule, (on palms and
soles)???The dark-colored macule due to the accumulation of a melanin- like substance in the
fungus. Lesions are non-inflammatory and non-scaling.

https://www.uptodate.com/contents/tinea-nigra#:~:text=Tinea%20nigra%20is%20a%20superficial,(picture%202A%2DC).
 Diagnosis:
- Direct microscopy of skin scrapings mounted in 10% KOH showing pigmented brown to dark
olivaceous (dematiaceous) septate hyphal elements and 2-celled yeast cells producing
annelloconidia typical of Hortaea werneckii.
The 2-celled structure become elongated hyphae by aging, i.e., dimorphic. Older cultures both
mycelia and conidia predominate i.e., spore forming.
- A fungal culture on Sabouraud's agar media produced mucoid brown colonies and become
dark green to black and shiny with time.
 3- Black piedra:
caused by Piedraia hortaie which colonizes hair shaft giving black??? hard nodule.
Diagnosis: clinically
and microscopically

4- White piedra: caused by Trichosporon beigelii, yeast - like fungus which affects the hair
producing soft white to creamy yellow granules that form a sleeve like collarets along the hair
shaft .

Diagnosis: clinically and microscopically (arthroconidia and blastoconidia are detected ).

Treatment of superficial mycosis :
Examples of treatments:
- topical keratolytic agents such as, hyposulfite, salicylate, and thiosulfate to remove the
organism from skin.
- Also, antifungal agents (topically) e.g. miconazole are used.
- Shaving or cropping the infected hair close to scalp surface is beneficial in treatment of
superficial hair infections .
- Systemic antifungal??
II- Cutaneous mycoses :
Infections occur deeper into epidermis and invasive hair and nail diseases. Fungi are
belonging to several species which named dermatophytes, hence infections called
dermatophytoses (ringworm or tinea).

a- Microsporum: are common in scalp hair and transmitted to human from animals
(zoonoses) and soil. Also, it affects skin and transmitted from human another .
b- Trichophyton: are common in scalp hair, skin and nails and transmitted from human to
human and from animal to human (zoonoses).
c- Epidermophyton: are common in skin (groin) and nails .Only its transmission is common
among human (anthropophilic).
The dermatophytes vary markedly from ecologic niche to another .
a- Geophilic dermatophytes: isolated from soil.e.g. M. cookei
b- Zoophilic dermatophytes: associated with domestic and wild animal and birds e.g. M. canis,
M. equinum and T. equinum (zoonoses).
c- Anthropophilic dermatophytes: associated with human e.g. T. rubrum, M. audouinii and
most of epidermophyton.
 Pathogenesis:
Dermatophytes are keratinolytic. It produce keratinases which lysis keratin that used as a
substrate, however, it is not essential substance of growth. It does not able to invade other organ
than keratinized layer. Natural resistance is recommending in some individuals. Resistant to
dermatophytoses may relate to Hormonal factors (fugistatic) and Cell - mediated immunity.

Examples of Tinea are :

-Tinea pedis(feet) - Tinea capitis(Scalp).
Tinea manuum (hands) - Tinea unguium (nails).
Tinea corporis (body). - Tinea cruris (groin).

Tinea capitis predominates in infant and children up to puberty, particularly native Indian and in
blacks .Tinea pedis predominates in adult . Tinea pedis and tinea capitis are more common in
men than women.
What is athlete’s foot?
What is Onychomycosis?
 Laboratory diagnosis :
The importance of identification of dermatophytes species may help to determine the possible
source of infections, if it anthropophilic, zoophilic or geophilic
Skin and nail scrapings or hairs taken from areas suspected to be infected are examined
microscopically using KOH (to clear from epithelial cells and other debris).
Dermatophytes appear as branched septet hyphal elements in specimen of cutaneous
lesion and nails .
In infected hairs treated with caustic alkali, fungus elements appear as spore inside (endothrix
infection) or surrounding (ectothrix infection) the air shaft .
Cultivation on Sabouroud's dextrose agar. Cultures that not produce growth are routinely held
for 4 weeks before being discarded as negative
 Treatment :
Examples:
Topical Azole derivative antifungal agents e.g. miconazole, clotrimazole, Ketoconazole
Topical allylamines: Terbinafine
Oral : griseofulvin, Terbinafine, Itraconazole, Fluconazole

https://www.cdc.gov/fungal/diseases/ringworm/treatment.html
II- Subcutaneous mycoses :
It characterized by development of lesions, usually at sites of trauma and implantation of foreign
bodies .
It occurs on feet, legs, hand, arms, where trauma is more common. Fungi found in soil and
decaying vegetation are the causative agents.
Examples of Subcutaneous mycoses are :
1- Sporotrichosis: is caused by Sporothrix schenkii as nodular and ulcerative lesions on
hand and other part of the body. Colonies of media at 25 C have delicate radiating forms that
appear as white at first but turned black with prolonged incubation.
Microscopic examination reveals branched hyphae with numerous conidia in a rosette pattern
at the end of conidiophores.
Sub-culturing at 37 C giving yeast form

Microscopic examination illustrating a flowerlike

arrangement" rosette pattern of Sporothrix schenckii
3 - Mycetoma: Clinical examination shows indolent, deforming, swollen lesions contain
numerous draining sinus tracts. When the causative agents are fungi mycetoma is called
eumycotic mycetoma .
•“Mycetoma is a chronic, progressively destructive infectious disease of the subcutaneous
tissues that spreads to affect the skin, deep tissues and bone.
•Mycetoma can be caused by different species of bacteria or fungi. Mycetoma is a chronic
disease usually of the foot but any part of the body can be affected. Infection is most probably
acquired by traumatic inoculation of fungi or bacteria into the subcutaneous tissue. So far more
than 70 different bacteria and fungi have been indicated as causative agents.”

https://www.who.int/news-room/fact-sheets/detail/mycetoma
 Treatment (Examples) :
Sporotrichosis: itraconazole (oral) - Oral potassium iodide saturated solution and I.V.
amphotericin B.
Chromoblastomycosis:
- “oral itraconazole or terbinafine. Voriconazole, IV amphotericin B and oral flucytosine
have also been used”.
- “Other methods of treatment include local application of heat, cryotherapy and
photodynamic therapy”.
- Surgery
Mycetoma: antibiotics for bacterial mycetoma, while mycotic one needs “long-term antifungal
medicine, but treatment may not be completely effective. In this case, surgery or amputation
are sometimes needed to cut away the infected tissue.”.
https://www.cdc.gov/fungal/diseases/sporotrichosis/index.html#:~:text=The%20most%20common%20treatment%20for,used%20if%20you%20are%20pregnant.
https://www.who.int/news-room/fact-sheets/detail/chromoblastomycosis#:~:text=not%20transmit%20chromoblastomycosis.-
,Treatment,heat%2C%20cryotherapy%20and%20photodynamic%20therapy.
https://www.cdc.gov/fungal/diseases/mycetoma/index.html#:~:text=The%20treatment%20for%20mycetoma%20includes,shoes%20might%20help%20prevent%20m
ycetoma.
 IV- Systemic mycosis :
Which organs are affected?
All causative agents reproduce sexually (parasitic phase, at 37 C) and asexually (saprobic
phase, at 25 C, culture and soil), except cryptococcus neoformans which reproduces
asexually only .

Examples of systemic mycosis are:

Diseases Agents
Histoplasmosis ................................... Histoplasma capsulatum
Blastomycosis ..................................... Blastomyces dermatitidis
Paracoccidioidomycosis ........................ Paracoccidiodes brasiliensis
Coccidioidomycosis .......................... Coccidioides immitis
Cryptomycosis .................................... Cryptococcus neoformans
 Diagnosis: Fungal morphology in both saprobic and parasitic phase is detected
microscopically. The antibodies raised against deferent fungi are detected using the specific
antigens in both free culture filtrate from mycelial phase growth and inactivated whole yeast .
Diagnosis of cryptomycosis is based on detection of antigen using latex agglutination test.
Treatment (examples):
Ketoconazole and other new azoles are used in systemic mycosis.
Amphotericin B and Itraconazole in treatment of histoplasmosis.
cryptomycosis : 5-fluorocytosine, Amphotericin B, fluconazole . In case of cerebrospinal
infection with cryptomycosis, 5-fluorocytosine is used because amphotericin B has poor
penetration into cerebrospinal fluid. Combination between these two drugs is highly effective to
overcome the development of resistance C. neoformans .
N.B. flucytosine = 5-fluorocytosine
https://www.cdc.gov/fungal/diseases/histoplasmosis/treatment.html#:~:text=Itraconazole%20is%20one%20type%20of,3%20months%20to%201%20year.&
text=Many%20people%20will%20need%20antifungal%20treatment%20for%20histoplasmosis.
https://www.cdc.gov/fungal/diseases/cryptococcosis-
neoformans/treatment.html#:~:text=For%20people%20who%20have%20severe,time%20to%20clear%20the%20infection.
 V- Opportunistic mycoses:
The fungal infections with low pathogenic potential and that produce disease when???

a- Candidiasis (Moniliasis): The etiology is genus Candida e.g. C. albicans is frequently carried
by man, usually in small amounts in the mouth, nose, throat, bowel, vagina, and on skin .
Under certain conditions e.g., in the presence of glycosuria, following the use of systemic or local
antibiotics and chemotherapy, especially immunosuppressive drugs, and the use of the
contraceptive pill, which may alter the local ecology and remove normal competitors), the fungus
may overgrow. This results in vulvar soreness and irritation and a vaginal discharge like cream
cheese, or in burning and irritation when it occurs in the rectum .
Candidiasis can be a cause of recurrent balanitis in the male partner and occasionally of
urethritis.
Treatment : Examples: by antifungal (e.g. nystatin, miconazole, fluconazole).

Diagnosis:
-Budding yeast; under microscope.
-Germ tube; when grown for 2 hr in presence of serum
at 37 C.
-It forms chlamydospores on corn meal agar at 25 C.

https://www.cdc.gov/fungal/diseases/candidiasis/thrush/index.html#:~:text=Treatment-
,Candidiasis%20in%20the%20mouth%2C%20throat%2C%20or%20esophagus%20is,usually%20treated%20with%20antifungal%20medicine.&text=The%2
0treatment%20for%20mild%20to,clotrimazole%2C%20miconazole%2C%20or%20nystatin.
b- Aspergillosis: Caused by various species of Aspergillus e.g. A. flavus and A. fumigatus
cause both allergic and systemic aspergillosis .

c- Zygomycosis (Mucormycosis): Caused by Mucor and Rhizopus .