Fungal infections part I

INTRODUCTION TO FUNGAL INFECTIONS, Classification of Fungal Infections (mycoses), Pityriasis versicolor, Tinea nigra, Black piedra, White piedra 

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3. INTRODUCTION TO FUNGAL INFECTIONS

4. INTRODUCTION TO FUNGAL INFECTIONS Historically it was thought that fungi were plants that did not need photosynthesis. But now fungi are classified in their own kingdom, separate from plants and animals because: 1- The cell walls of plants are made of cellulose whereas the walls of fungal cells are made of chitin 2- Plants require only simple inorganic compounds such as carbon dioxide and water to grow. Fungi require a diet of complex organic molecules to thrive. Fungi are parasites or saprophytes i.e. they live off living or dead organic matter.

5. INTRODUCTION TO FUNGAL INFECTIONS Growing fungi have branched filaments called hyphae, which make up the mycelium (like branches are part of a tree). Hyphae are threadlike filaments made up of fungal cells, whereas mycelium is the mass of hyphae that forms the fungal body . Some fungi are compartmented by cross-walls (called septae ). Arthrospores are made up of fragments of the hyphae, breaking off at the septae . Asexual spores (conidia) form on conidiophores. The sexual reproductive phase of many fungi is unknown; these are ‘fungi imperfecta ’ and include those which infect humans.

6. INTRODUCTION TO FUNGAL INFECTIONS FORMS OF HYPHAE; Septate hyphae: In most fungi, hyphae are divided into cells by internal cross-walls for example “ Aspergillus ”. Coenocytic hyphae (non- septate hyphae): meaning their hyphae are not partitioned by septa. Pseudo hyphae : They are the result of incomplete budding where the cells remain attached after division, and Yeast can form pseudohyphae .

7. INTRODUCTION TO FUNGAL INFECTIONS Yeasts form a subtype of fungus characterized by clusters of round or oval cells. These bud out similar cells from their surface to divide and propagate. In some circumstances they form a chain of cells called a pseudomycelium .

8. conidiophore

9. INTRODUCTION TO FUNGAL INFECTIONS THE ORGANISMS ARE TRANSMITTED BY EITHER; Direct contact with infected host (human or animal ). Indirect contact with infected exfoliated skin or hair in combs, hair brushes, clothing, furniture, theatre seats, caps, bed linens, towels, hotel rugs, and locker room floors.

10. Classification of Fungi According to their appearance by microscopy and in culture or method of reproduction. BY THE METHOD OF REPRODUCTION: Sexual Asexual.

11. SUPERFICIAL MYCOSES Non-inflammatory Inflammatory SUBCUTANEOUS MYCOSES SYSTEMIC MYCOSES Classification of Fungal Infections (mycoses)

12. I. SUPERFICIAL FUNGAL INFECTIONS

13. I. Superficial fungal infections These affect the outer layers of the skin, the nails and hair. The main groups of fungi causing superficial fungal infections are: Yeasts Candida Malassezia Dermatophytes ( ringworm/tinea ) Other Moulds e.g. Aspergillus spp. Fusarium spp.

14. I. Superficial fungal infections Infections limited to the outermost layers of the skin and hair: Pityriasis versicolor Candidiasis   Tinea nigra   Black piedra White piedra  

15. I. Superficial fungal infections Infections that extend deeper into the epidermis, as well as hair and nail and caused by dermatophytes . They colonize the keratin and inflammation is caused by host response to metabolic by-products: Tinea capitis (head ) Tinea faciei (face) Tinea barbae (beard) Tinea corporis   (body) Tinea manus (hand) Tinea cruris (groin) Tinea pedis (foot) Tinea unguium (nail)

16. I. Superficial fungal infections THE MAIN 3 GENERA OF DERMATOPHYTES ARE: T richophyton (abbreviated as "T") E pidermophyton (“E") M icrosporum (“M")

17. Classification of dermophytes according to habitat Anthropophilic dermatophytes are restricted to human hosts and produce a mild, chronic inflammation e.g. T. rubrum ▪ M. audouinii T . interdigitale ▪ T . violaceum T. tonsurans ▪ T . schoenleinii Zoophilic organisms are found primarily in animals and cause marked inflammatory reactions in humans who have contact with infected cats, dogs, cattle, horses, birds, or other animals e.g. M . canis (originating from dogs and cats) T. equinum (originating from horses) T . verrucosum (originating from cattle) Geophilic species are usually recovered from the soil but occasionally infect humans and animals. They cause a marked inflammatory reaction, which limits the spread of the infection and may lead to a spontaneous cure but may also leave scars e.g. M . gypseum M. fulvum

18. II. SUBCUTANEOUS FUNGAL INFECTIONS

19. II. Subcutaneous fungal infections These involve the deeper layers of the skin (the dermis, subcutaneous tissue, muscle & fascia and even bone). The causative organisms normally live in the soil living on rotting vegetation. They can get pricked into the skin as a result of an injury but usually stay localized at the site of implantation. Deeper skin infections include: Mycetoma Chromoblastomycosis Sporotrichosis

20. III. SYSTEMIC FUNGAL INFECTIONS

21. III. Systemic fungal infections May result from breathing in the spores of fungi, which normally live in the soil or rotting vegetation or as opportunistic disease in immune compromised individuals. A. Inhaled fungal infection (By True pathogens) Although uncommon, some may infect healthy individuals. The result is most often a mild infection and long lasting resistance to further attack, but occasionally these infections are more serious and chronic (especially in the immune suppressed). The organisms causing systemic fungal infections include: Histoplasmosis Coccidioidomycosis (North and South America). B. Opportunistic infections Other systemic mycoses only infect those who are already sick or with an immunodeficiency disorder i.e. they are ‘opportunists’. Repeated infection may occur. Risks for systemic mycoses include: Serious illness and debility Cancer or leukemia Diabetes mellitus Transplant Massive doses of antibiotics Parenteral nutrition Drug addiction Infection with human immunodeficiency virus (HIV) Opportunistic fungal infections include: Aspergillosis (found everywhere) Zygomycosis Cryptococcosis (where there are pigeon droppings) Trichosporon beigelii Pseudallescheria boydii

22. PITYRIASIS ( TINEA) VERSICOLOR

23. PITYRIASIS VERSICOLOR (PVC) It is a common, long-term (chronic) superficial fungal infection of the skin . Affected skin change color and become either lighter or darker than surrounding skin.

24. Epidemiology of PVC Common in adolescent and young adult males . Malassezia requires oil to grow, accounting for the increased incidence in adolescents and preference for sebum-rich areas of the skin. Its occurrence before puberty or after age 65 years is uncommon . A member of normal human cutaneous flora , and it is found in 18 % of infants and 90-100 % of adults and it is NOT CONTAGIOUS .

25. Epidemiology of PVC Worldwide distribution but prevalence reported to be as high as 50 % in the humid , hot environment and as low as 1.1 % in the colder temperatures. The condition is more noticeable during the summer months.

26. Pathogenesis of PVC The causative fungus is Malassezia furfur (previously known as Pityrosporon orbiculare and Pityrosporon ovale ). In patients with clinical disease , the organism is found in both the yeast stage and the filamentous ( mycelial /hyphae ) form. Factors that lead to the conversion to the parasitic, mycelial morphologic form include; Genetic predisposition Oily skin (yeast is lipophilic) Excessive sweating Warm, humid environments Immuno-suppression Malnutrition Pregnancy Cushing disease

27. Pathogenesis of PVC The reason why this organism causes PVC in some individuals while remains as normal flora in others is not entirely known . Several factors, such as the organism's nutritional requirements and the host's immune response to the organism, are significant. Lymphocyte function on stimulation with the organism has been shown to be impaired in patients who are affected.

28. Pathogenesis of PVC Decreased pigmentation may be secondary to the inhibitory effects of dicarboxylic acids on melanocytes ( these acids result from metabolism of surface lipids by the yeast ). Sun exposure may make PVC more apparent . Decreased tanning , due to the ability of the fungus to filter sunlight . The yeasts induce enlarged melanosomes within melanocytes in the brown type of PVC.

29. Clinical features of PVC Pityriasis versicolor is usually asymptomatic , but in some people it is mildly itchy. Numerous , well- marginated , finely scaly , oval-to-round macules . Demonstration of this associated scale may require scratching or stretching the skin surface.

30. Clinical features of PVC Scattered over the trunk , shoulders and/or the chest , the proximal extremities with occasional extension to the lower part of the abdomen and the neck . Less frequently, lesions are seen on the face (especially in children ), scalp .

31. Clinical features of PVC The macules tend to coalesce , forming large irregularly shaped patches .

32. Clinical features of PVC As the name versicolor implies, the color of each lesion varies from almost white , pink (mildly inflamed), tan to dark brown

33. Clinical features of PVC An INVERSE form also exists affecting the flexural regions antecubital fossae , sub-mammary region and groin .

34. Clinical features of PVC Sometimes the patches start scaly and brown , and then resolve through a non-scaly and white stage .

35. Diagnosis of PVC Usually diagnosed clinically . Wood’s light examination ( revealing bright yellow- green fluorescence ).

36. Diagnosis of PVC SKIN SCRAPING: then it is examined under a microscope. DIRECT MICROSCOPY: Skin scrapings taken from patients with PVC stain rapidly when mounted in 10% KOH , glycerol and Parker ink solution and show characteristic clusters of thick-walled round , budding yeast-like cells and short angular hyphal forms up to 8um in diameter (SPAGHETTI WITH MEATBALLS APPEARANCE) . These microscopic features are diagnostic for Malassezia furfur and culture preparations are usually not necessary .

37. Diagnosis of PVC CULTURE: is only necessary in cases of suspected fungaemia .  M. furfur  is a lipophilic yeast , therefore in vitro growth must be stimulated by natural oils or other fatty substances. The most common method used is to overlay Sabouraud's dextrose agar containing cycloheximide ( actidione ) with olive oil or alternatively to use a more specialized media like Dixon's agar which contains glycerol mono- oleate (a suitable substrate for growth).

38. Histopathology of PVC Biopsies are usually not performed , as KOH examination of associated scale is typically diagnostic. This section shoes; Hyperkeratosis without parakeratosis Few inflammatory cells in the epidermis Numerous yeast & plump hyphae

39. DDx of PVC Pityriasis alba Postinflammatory hypopigmentation Vitiligo Seborrheic dermatitis Pityriasis rosea Tinea corporis Secondary syphilis Progressive macular hypomelanosis

40. Treatment of PVC TOPICAL TREATMENT Azole creams and lotions; Clotrimazole , Ketoconazole, Miconazole Dandruff shampoos Ketoconazole (1% or 2%) or 2.5% selenium sulfide twice weekly for 2 to 4 weeks; the preparation is left on the skin for 10–15 minutes before rinsing. Over-the-counter dandruff shampoo contain heavy metals e.g. Zinc, Mercury, Copper e.t.c .  inhibition of growth of any fungi by reacting in their biosynthetic pathways. Treatment of all the skin from the neck down to the knees , even if only a small area is clinically involved. Allylamine Nystatin Salicylic acid Sodium thiosulphate solution Ciclopirox cream/solution 50% propylene glycol in water

41. Treatment of PVC SYSTEMIC TREATMENT If the rash is extensive, oral antifungal medications may be needed they are; Fluconazole (300 mg once weekly for 2 weeks) Itraconazole (200 mg daily for 5-7 days) Ketoconazole (200 mg 5 days-5 weeks), Vigorous exercise an hour after taking the medication may help sweat it onto the skin surface, where it can effectively eradicate the fungus. Avoid bathing for a few hours.

42. Prognosis & Prevention of PVC Though it is easily treated, pigment changes may last for months after treatment. Because this rash has a high recurrence rate , medication may be needed periodically to prevent recurrence . The rate of recurrence of pityriasis versicolor is very high, especially in hot humid climates so avoid heat in hot weather . Patients at high risk for recurrence may be helped by using ketoconazole shampoo once weekly as a body cleanser. Another preventative measure is once-monthly dosing of oral ketoconazole (400 mg), fluconazole (300 mg) or itraconazole (400 mg).

43. Tinea Nigra

44. Etiology of Tinea Nigra It is due to infection by the fungus, Hortaea werneckii . Occurs as a result of inoculation from a contamination source such as soil sewage , wood , or compost subsequent to trauma in the affected area. Note the 2 celled yeast forms

45. Epidemiology of Tinea Nigra Typically occur in tropical climates such as Central and South America, Africa, Asia and, occasionally, in the southeastern US.

46. Pathogenesis of Tinea Nigra No predispositions have been identified . Typically , the incubation period is 10- to 15-day . A pigmentary change in the skin results from the accumulation of a melanin-like substance in the fungus.

47. Clinical features of Tinea Nigra Asymptomatic brown -to- black sharply marginated macule or patch , resembling silver nitrate or India ink stains. The surface may appear mottled , velvety or have mild scale . The lesions are typically solitary , although may be multiple . Although most frequently seen on the palms , tinea nigra can also appear on the soles , neck and trunk .

48. Clinical features of Tinea Nigra The shape of the lesion varies, and they may appear ovoid , round , or irregular . The lesion slowly grows over weeks to months. The size may range from a few millimeters to several centimeters in diameter , depending on the duration. It may have darker pigmentation of the advancing border as compared to the center. While the disease tends to be chronic , recurrence after effective treatment is infrequent except in the case of re-exposure .

49. Diagnosis of Tinea Nigra KOH EXAMINATION reveals highly branched and septate pigmented hyphae. BIOPSY specimens have similar findings observed within the stratum corneum. CULTURES of H. werneckiifirst appear as pasty, green-black colonies with a yeast-like appearance, and then change after approximately 2 weeks to a fuzzy, dematiaceous (dark in color) mold.

50. DDx of Tinea Nigra Acral melanocytic nevi. Fixed drug eruption. Postinflammatory hyperpigmentation. Staining from chemicals, pigments and dyes. Melanoma.

51. Treatment of Tinea Nigra Topical keratolytic agents such as Whitfield’s ointment (typically 6% benzoic acid plus 3% salicylic acid) Topical azole Topical Allylamine Several weeks of therapy may be required to prevent recurrence of disease . Systemic therapy is generally not indicated.

52. PIEDRA (TRICHOMYCOSIS NODULARIS)

53. PIEDRA It is a superficial non-inflammatory nodular fungal infection confined to hair shafts. “Piedra” means “ stone ”, reflecting the fungal elements’ adherence to one another to form nodules along the hair shaft, the surrounding skin is healthy . Favored climate; tropical areas. There are 2 types Black Piedra & White Piedra .

54. BLACK PIEDRA WHITE PIEDRA CAUSATIVE FUNGI Piedraia hortae Trichosporon beigelii (6 pathogens) PATHOGENESIS Infection usually begins under the cuticle of the hair shaft and extends outward . Hair breakage may occur as a result of shaft rupture at the site of the nodules. As the nodules enlarge, they can even envelope the hair shaft . Infection also begins beneath the cuticle and grows through the hair shaft, causing weakening and breakage of the hair .

55. CLINICALLY BLACK PIEDRA WHITE PIEDRA NODULE COLOR Brown to black along the hair shaft. Generally white but may also be red , green or light brown in color. NODULE FIRMNESS Hard Soft NODULE ADHERENCE TO THE HAIR SHAFT Firm Loose TYPICAL ANATOMIC  LOCATION Face, axillae and pubic region (occasionally scalp) Scalp and face (occasionally pubic region its incidence has increased since the start of the HIV pandemic) SYSTEMIC INFECTION Non In immunosuppressed patients , T. beigelii can cause TRICHOSPORONOSIS , a serious with f ungemia , f ever, pulmonary in f iltrates, skin lesions ( papulovesicular and purpuric , often with central necrosis) and renal disease.

56. INVESTIGATIONS BLACK PIEDRA WHITE PIEDRA KOH EXAMINATION “crush preparation” Dematiaceous hyphae Organized cluster of asci , each of which contains eight ascospores ( sexual phase of P . hortae - the only sexual phase detected that is pathological to human ) Non- dematiaceous hyphae Blastoconidia and arthroconidia (representing the asexual state ) CULTURE ON SABOURAUD’S AGAR Very slow-growing Dark green to dark brown – black colonies with a velvety texture (asexual phase) Grows rapidly Moist, cream-colored , yeast-like colonies Cycloheximide inhibits growth.

57. DDx OF PIEDRA Pediculosis (nits) Hair casts Trichorrhexis nodosa Trichomycosis axillaris Scaly scalp conditions

58. Treatment of piedra Clip affected hairs. Wash affected hairs with antifungal shampoo 2% ketoconazole shampoo or selenium sulfide. Topical imidazole cream. Oral ter b inafine may also be used for b lack piedra. Oral it raconazole may also be used for wh it e piedra.

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