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1 number 19 Done by عمرسامي Corrected by حسام أبو عوض Doctor حامد الزعبي

2 Fungal infections - Fungal infections are infections caused by fungi, a type of microorganisms. Which sites are mostly affected? - Mainly, the Skin and subcutaneous tissues are affected, systemic infections are not common. Throughout this lecture, we will be discussing the Superficial, Cutaneous & Subcutaneous fungal infections and the fungi which cause each one of them. Mainly caused by: Malassezia. Superficial Infections Malassezia: a Lipophilic yeast that is round in shape. It is a Normal commensal of the skin (normal flora). It Can cause skin infections and catheter associated infections (mainly skin infection in immunocompetent patients & catheter associated infections in immunocopromised patients). Immunocompetent vs immunocompromised - An Immunocompromised patient is (immunology) the one with an impaired immune system due to a disease or a treatment, while an immunocompetent patient has a normally functioning immune system. Diseases caused by Malassezia - Pityriasis versicolor or Tinea versicolor: A fungal infection characterized by skin eruption on the trunk and proximal extremities. - Located mainly on the stratum corneum of the skin the outermost layer of the epidermis. - Trunk and proximal limbs are also affected. Caused mainly by: Malassezia furfur and Malassezia globose The Classical Diagnostic Situation The disease is common in the tropics and is precipitated by sun exposure (usually occur after the patient gets exposed to sunlight).

3 Patches may be white, pink, red or brown and can be lighter or darker than the skin around them; Carboxylic acid, which is produced by the yeast, causes depigmentation, either hypo OR hyper pigmentation. When the patient arrives to the clinic, what are the main features to be noticed? Asymptomatic. Non-itchy macules (at the level of the skin, not elevated). Hypo or hyper pigmented patches. We can use either microscopic or non-microscopic techniques (we can also consider the patient s history, e.g. have they gone to the beach recently?) Non-Microscopic How to make sure that it is Malassezia? - Physicians & dermatologists often use a technique to ensure whether it is M. furfur or not, they use the Wood ultra-violet lamp test, here M. furfur appears in a light pale greenish colour. A Wood lamp examination: is a test that uses ultraviolet (UV) light to look at the skin closely. Microscopical How is it performed? - Skin scraping Ink KOH staining. How does it appear? - Thick septate* hyphae** and clusters of budding yeast cells (Spaghetti and meatballs spores and hyphae) which is a special appearance for Malassezia. *septate: divided to septums. **hyphae: thread-like, filamentous structures of fungi. Usually not needed, however the patient may ask for it for cosmetic purposes. - Topical azoles (cream or a shampoo) for 2 weeks.

4 - In severe cases use oral azoles. - Recurrence is common. (االكزيمة الدهنية) Seborrheic dermatitis - This is another disease that can be caused by Malassezia. - Skin hyperproliferation with dandruff (قشرة) is the mildest manifestation. - In more severe cases, lesions are red and covered with greasy scales, hair loss is seen and an itchy scalp is common. Azoles. We have finished the first group, superficial mycosis. Take a five-minute break then let s continue I said five minutes - - Cutaneous Mycosis - Caused by: Dermatophytes [filamentous fungi ( خيوط فطرية ( /moulds] - This includes 3 genera Microsporum affects hair and skin. Epidermophyton skin and nail. Trichophyton hair, nail and skin. These fungi affect the keratinized tissues such as skin, hair & nails they are thought to have keratinase to disrupt keratin at this site of the body. Note: Infection is usually not spread to deeper tissues. How is it transmitted? 1- Man to man: by direct contact, skin contact (Anthrophilic) or by the usage of the personal belongings of an already infected individual. 2- Animals e.g. dogs and cats (Zoophilic). 3- Soil (Geophilic). ** Heat and humidity enhance the infection. They are also classified according to the site of infection Site Disease

5 Toes Tinea pedis or Athletic foot Body (mainly trunk) Tinea corporis Groin area Tinea cruris Head tinea capitis Nails Tinea unguinum Clinically Red, itchy, scaly rash (dandruff in the middle), ring like with an elevated inflamed border on the body or groin. Scaling and hair loss leaving black dots, if it is in the head. White and opaque / yellow, thickened & broken nails. Differential diagnosis - What is a differential diagnosis? - Distinguishing a particular disease or condition from others that present similar symptoms. So, cutaneous mycosis is usually miss-diagnosed with one of the following; due to similar symptoms and manifestations. Eczema, psoriasis, impetigo, alopecia, drug reactions. 1- Microscopic examination - Skin scales, nail & hair are examined microscopically after digesting using 10% KOH. - Hyphae or spores are detected in the hair. - Spores are detected either inside the hair (endothrix) or outside the hair (ectothrix) Hair examination - Shaft ectothrix - bulb endothrix 2- Culture - Cultured in Sabouraud s dextrose agar SDA and incubated at room temperature for 4 weeks.

6 - The arising colonies are examined microscopically after staining with lactophenol cotton blue stain. Always REMEMBER The medium SDA. The stain Lactophenol cotton blue stain. - Local antifungal cream (miconazole). - Keep the infected area dry; moisture helps these fungi to grow. - Nail infections need a long treatment through Oral Administration of Terbinafine for 3-6 months (difficult to treat). Microsporum, Trichophyton & Epidermophyton Species - Special traits Microsporum: Thick Wall, spindle shape, multicellular. Trichophyton: Thin Wall, pencil-shaped, large, smooth appearance with septums. Epidermophyton floccosum: Bifurcated hyphae with multiple, smooth, club shaped macroconidia (2-4 cells) Candidiasis Candida albicans is the most important and most common species of candida. Candida albicans is an oval gram-positive budding (way of replication) yeast which produces pseudo-hyphae (species include: C. glabrata and C. krusei). It colonizes the mucous membranes of the upper respiratory tract, GIT & female genital tracts. (Normal flora in 3% of the people) It usually causes superficial infections on the skin and mucous membranes. It may predominate and spread towards the systems in immunocompromised patients. Predisposing factors to Candida infections Patients with AIDS & diabetes mellitus. Drugs: prolonged treatment with broad spectrum antibiotics & corticosteroids. General disability. Indwelling urinary catheters.

7 Pathogenesis & Symptomatology 1- Skin invasion Thus, it is called the opportunistic fungi. They are red & weeping lesions, like ulcers. Mainly affect warm moist areas; axilla, intergluteal folds or infra mammary folds (or any other fold). Mostly in obese & diabetic patients. Pseudo-diaper rash for the baby. Usually misdiagnosed as a bacterial infection, impetigo, Fucidin won t show any effect, the condition remains there until the right treatment is given (local azoles). 2- Mouth infection C. albicans produces white patches in the mouth, like the mucous membrane (oral thrush or moniliasis). 3- Vulvovaginitis - Usually in pregnant women; due to hormonal changes. - Usually with itching & thick vaginal discharge. - Common with diabetic woman & prolonged use of antibiotics. - IUCD (intrauterine device), contraceptive method. 4- Nail infection Thick, yellow, weak and can easily be removed from its place. 5- Systemic candidiasis In immunocompromised. Direct Microscopic Examination Specimens from skin, vaginal discharge or exudates from mucous surfaces are examined or you can even examine the blood if you suspect a candidemia and you should see oval gram positive budding yeast celsl with pseudohyphae.

8 Culture Can be grown on nutrient agar, corn meal agar & SDA (Sabouraud s dextrose agar SDA) Identified by 1- Morphology Oval budding gram positive yeast cells. 2- Differentiation tests a. Germ tube test: germ tubes are formed when colonies are incubated with human serum at 37 C for 30 min. b. Chlamydospore formation on corn meal agar. c. Biochemical reactions: C. albicans ferments glucose & maltose with acid & gas production. differs according to the site of infection - Oropharyngeal or esophageal thrush local treatment: Nystatin Fluconazole ointment. - Skin lesions local treatment: Nystatin ointment. - Systemic candidiasis you have to use a systemic treatment (Caspofungin IV, Ketoconazole (orally) Amphotericin B (IV) ) Subcutaneous Mycosis Mycetoma (Madura foot): Mycetoma is a chronic infection of skin and subcutaneous tissues. - These infections are caused by fungi that grow in soil & on decaying vegetations. - The fungi are introduced into the subcutaneous tissues through trauma. Pathogenesis: granulomatous lesions due to proliferation and body response. The disease usually affects farmers.

9 Diseases 1- Eumycetoma: caused by the fungi Madurella mycetomatis, this is characterized by having true septate hyphae. 2- Actinomycetoma: it is a bacterial infection, rare & caused by species of actinomycetes. The symptoms are close to those of eumycetoma. (Filamentous aerobic bacteria). Clinically Swelling following trauma, purplish discoloration & multiple sinuses that drain pus containing yellow, white, red or black granules or black discharge. Note: Disfigurement of the organ might also occur due to the granulomas. E.g. Madura foot. Macroscopic examination Depend on the color of the granules Black granules are common with fungal infections (sinuses with pus are also noted). Microscopic examination - Septate hyphae with spores in fungal infection. Culture: on SDA 1.Medical: - ketoconazole - Itraconazole - Amphotericin B 2. Surgical intervention. Cryptococcus Neoformans Cryptococcus neoformans causes cryptococcosis. A widespread encapsulated yeast that inhabits soil around pigeon roosts. Commonly infects patients with AIDS, cancer or diabetes (immunocompromised patients) opportunistic infection. it starts by infecting the lungs by inhalation from the environment; it leads to cough, fever, and lung nodules fungal pneumonia.

10 Dissemination to meninges and brain can cause severe neurological disturbance and death. - Microscopic India ink for capsule stain, special stain (50-80% + CSF) (you need to order this stain specifically, it is not a common test). - Culture Bird seed agar Routine blood culture - PCR Aspergillosis Diseases of the Genus Aspergillus Very common airborne soil fungus. 600 species, 8 involved in human diseases; caused mainly by A. fumigatus. Serious opportunistic threat to AIDS, leukemia, and transplant patients the spores are present in the environment; only immunocompromised patients are affected. Note: immunocompetent individuals will have an asymptomatic infection and the body will soon terminate the infection OR they may develop Bronchopulmonary allergy, asthma or even exacerbation of asthma in already asthmatic patients. The infection usually occurs in the lungs, spores germinate in the lungs and form fungal balls; can colonize sinuses, ear canals, eyelids, and conjunctiva. Bronchopulmonary allergy (in immunocompetent) or Invasive aspergillosis (in immunocompromised) usually affect preformed cavities in lungs due to previous infection of TB or abscess, these fungi replicate within these cavities producing cotton like spheres which can cause a necrotic pneumonia, infection of the brain, the heart, and other organs (difficult to treat). Surgery, Amphotericin B and nystatin.

11 Zygomycosis - Usually in uncontrolled diabetic patients. - Opportunistic. - 3 involved genera; Rhizopus, Absidia, and Mucor. - Very invasive, invade the mucous membrane of the nose to the cerebra, if it reaches the brain it is usually fatal as it causes massive destruction to the tissue (poor prognosis). - Usually harmless air contaminants. They invade the membranes of the nose, eyes, heart and brain of the people (Rhinocerebral mucormycosis) with diabetes and malnutrition with severe consequences. Rhinocerebral mucormycosis is a rare opportunistic infection of the sinuses, nasal passages, oral cavity and the brain caused by saprophytic fungi. Made by direct smear and by isolation of molds from respiratory secretions or biopsy specimens. Control Diabetes, surgery & amphotericin B Prognosis Very poor Classical Case Diabetic patient with nose lesions & meningitis most likely it is zygomycosis.