Common fungal traits:

• Many are dematiaceous, aka, pigmented fungi.
  – It is thought that the melanin in their cells contributes to virulence.
• Many are dimorphic, which means they exist in both hyphal and yeast forms.
• Reside in soil, on plants, and decaying vegetation.
• Trauma to the skin introduces pathogenic fungi to the underlying tissues.
  – Thus, infections tend to occur on the extremities, especially the feet and hands, which are likely to be inoculated during gardening or field work.
• Chronic, granulomatous lesions in the skin and deeper tissue.
  – Often, histopathologic samples will show Splendore-Heoppliphenomenon, aka, asteroid bodies, which are characterized by eosinophilic materials radiating from the microorganisms.
• Initial lesion occurs at the site of inoculation, for example, in the skin of the feet
  – Then spreads to deeper tissues, which can include the lymphatics, muscles, and connective tissues.
• Rarely disseminate to other organs.
• Long-term antifungals can be used to treat some subcutaneous mycoses.

Lymphocutaneous sporotrichosis
“Rose Gardener’s Disease”
– Many individuals are inoculated via rose thorns.

• The fungi most often responsible are members of the Sporothrix schenckii complex.
• Mycosis manifests as linear cutaneous nodules and ulcers that begin at the site of inoculation and travel along the path of the draining lymphatics.
  – In some patients, the lesions will become suppurative; the discharged pus contains fungi that is useful for diagnostic purposes.

Chromoblastomycosis
Chromomycosis

• Caused by a variety of fungi
  – Fonsecae, Cladosporium, Phialophora, etc.
• Histopathologic samples show characteristic Medlar bodies (aka, sclerotic bodies or muriform cells).
  – Medlar bodies are cells with transverse septa and thick, pigmented cell walls; some liken them to copper pennies.
  In the sample, we can see some Medlar bodies within a giant cell.
• Chromoblastomycosis produces slowly developing, chronic lesions that can cause progressive tissue fibrosis.
  – Lesion morphology varies; for example, some patients have warty or “cauliflower-like” nodules, while others develop plaques with central scarring.
• Mild cases where warty nodules are involved may be cured by excision.
• However, excision is not practical in patients with extensive lesions, as we see in the example of plaques; thus, long-term antifungals are the preferred treatment in such cases.

Eumycotic Mycetoma
Madura foot or Maduramycosis

• Caused by Madurella mycetomatis and other fungi.
• Because mycetoma is also caused by bacteria, it’s important to culture samples from the patient to rule out actinomycetemycetoma, which requires a different intervention.
• Eumycotic mycetoma is characterized by painless nodules that progress to ulcers; the ulcers discharge fluid and granules.
  – Granules comprise the fungal hyphae
  – The color of the granule is indicative of the microorganism type
  M. mycetomatis granules are dark brownish-black.
• Eumycotic mycetoma is a chronic and progressive condition,and new sinuses form as older sinuses heal.
• The draining sinuses produce swelling and tissue deformity;infection can ultimately invade and destroy deeper tissues.
• Unfortunately, eumycotic mycetoma often responds poorly to antifungal treatments, so amputation is often necessary to prevent further destruction.

Subcutaneous Entomophthoromycosis

Conidiobolus coronatus

• Conidiobolomycosis most commonly affects adults.
• Inhalation produces infection in the nasal and paranasal sinuses.
• Swelling and deformity of the nose and upper lip can be quite dramatic, though relatively painless.

Basidiobolus ranarum

• Basidiobolomycosis more commonly affects male children.
• Produces “rubbery” dark lesions on the buttocks, thighs, and shoulders.
  – Gastrointestinal involvement is possible, though rare.

Subcutaneous Phaeohyphomycosis

• Various species
  – Exophiala, Bipolaris, Curvalaria, etc.
• Histopathologic samples are characterized by irregular hyphae.
• Infection produces slow growing cysts, or, sometimes, plaques.

Two key phyla:

Basidiomycota
– Specifically, species of Malassezia, which are yeast that colonize the superficial layers of the skin and hair.

• Because they do not invade or destroy living tissues, they generally do not trigger an immune response.
• Infections common in warm, moist environments.

Ascomycota
Dermatophytes are fungal pathogens that can invade the skin and cause dermatophytoses, such as ringworm.
– Dermatophytic species come from three genera:
Trichophyton, Epidermophyton, and Microsporum.
– These molds infect keratin of the skin, hair, and nails; because they cause damage to the tissues, they trigger an immune response.
– These fungi cause mycoses called tineas, aka, ringworm
Are acquired from contact with infected soil, animals, or other humans.

Laboratory diagnosis

• KOH (potassium hydroxide) testing, in which skin scrapings and KOH are viewed under microscope.
• Calcofluor white stain is also used to detect fungi in samples.
  – Fluorescent stain with affinity for the chitin in fungal cell walls.

Treatments

When necessary, treatments for superficial and cutaneous mycoses involves topical and/oral antifungals, in addition to good hygiene.

Mycoses

• Pityriasis versicolor
  Sometimes called tinea versicolor
• Caused by species of the Malassezia genus.
  – In the microscopic image we can see Malassezia cells and some short hyphae; some authors describe their appearance as looking like “spaghetti and meatballs.”
• Young adults in warm, moist environments are most likely to develop pityriasis versicolor.
• Fungi are spread via human to human contact.
• Lesions appear as either hypo- or hyper-pigmented, and typically appear on the upper body, face, and neck.

• Tinea nigra is caused by the fungus Hortaea werneckii
• In the microscopic image, we can see septate hyphae and budding cells.
• Tinea nigra is most common in children and young adults in tropical and subtropical climates.
• Manifests as patches of small dark dots, typically on the palms of the hands and soles of the feet.

• White piedra (piedra means “stone”) is caused by species of Trichosporon, which are yeasts that colonize the hair shaft.
• Individuals in tropical and subtropical areas are most likely to have white piedra.
• Manifests as soft white or cream-colored nodules on the hair shafts.

• Black piedra is caused by the yeast Piedra hortae, which colonizes the hair and scalp of individuals in tropical areas.
• It produces firm dark nodules in the hair.

• Tineas
  Commonly referred to as Ringworm.
• Caused by dermatophytic fungi.
• The tineas are named for their location on the body, as follows:
  – Tinea capitis develops on the scalp, especially of children, and is associated with alopecia, scaling, and cervical and suboccipital lymphadenopathy.
  – Tinea barbae is ringworm that occurs in areas of facial hair.
  – Tinea corporis is ringworm that appears on the trunk or extremities; it produces red rings with scaly skin and is pruritic (itchy).
  – Tinea cruris, aka, jock itch, is most common in adolescent and young males; it produces a rash on the upper thighs, but typically does not involve the scrotum.
  – Tinea pedis, aka, athlete’s foot, can involve all aspects of the feet:
  Interdigital is the most common, and involves the skin between the toes
  Moccasin tinea pedis is chronic and involves the sides and soles of the feet
  Vesicular tinea pedis is characterized by inflammation with vesicles and lesions
  – Tinea unguium is a fungal infection of the nails (thus, it is a type of onychomycosis).

Rickettsiaceae, Anaplasmataceae, Coxiellaceae

• Small, intracellular pathogens
• Obligate aerobes
• Gram-negative rods that stain best with Giemsa or Gimenez stains.
• Some infections caused by these species are self-limiting
  • Doxycycline can be administered to shorten illness duration and prevent complications.

Species overview

Be aware that all of these species were formerly categorized as members of Rickettsiaceae, and that intertextual variation exists.

Rickettsiaceae damages endothelial cells of blood vessels

• Rickettsia rickettsii causes Rocky Mountain Spotted Fever
• Rickettsia akari causes rickettsial pox
• Rickettsia prowazekii and Rickettsia typhi cause different forms of typhus
• Orientia tsutsugamushi causes scrub typhus.
  to damage to the endothelial cells of blood vessels.

Anaplasmataceae

• Ehrlichia chaffeensis causes human monocytic ehrlichiosis
• Ehrlichia ewingii causes human ewingii ehrlichiosis
• Anaplasma phagocytophilum causes human granulocytic anaplasmosis.

Coxiellaceae

• Coxiella burnetti causes Q fever.

INFECTIONS, RESERVOIRS, AND VECTORS

Rickettsia rickettsii

• Rocky Mountain Spotted Fever
  — Fever, headache, myalgias, and, sometimes, confusion (as a result of CNS involvement).
  — Patients commonly develop a macular rash that can progress to petechiae; the rash characteristically begins on the wrists and ankles, then spreads to the palms, soles, and trunk. This pattern of spread is a helpful distinguisher.
  — Gastrointestinal involvement is possible, and can cause abdominal pain, nausea, vomiting, and/or diarrhea.
  — Left untreated, disseminated vasculitis can lead to multi-organ failure.
• Ticks and rodents are key reservoirs; hard ticks are vectors.

Rickettsia akari

• Rickettsialpox
  — Typically less severe than Rocky Mountain Spotted Fever.
  — Patients experience fever and papulovesicular rash with eschars. Headaches and myalgia are possible.
  — Rodents are the reservoirs; mites are the vectors.

Rickettsia prowazekii

• Epidemic typhus
  — Brill-Zinsser disease is the result of latent infection that manifests years, even decades, later.
  — Patients experience fever, headache, chills, myalgia, and a macular rash that spreads from the trunk to the extremities.
  — CNS involvement is possible, and can present as confusion.
  — If left untreated, vasculitis can lead to multi-organ failure.
  — Humans are the main reservoir, and the human body louse is the vector; be aware that flying squirrels and their fleas have also been described as reservoirs and vectors.

Rickettsii typhi

• Endemic typhus (aka, murine, typhus)
  — Patients experience fever, headache, myalgia, and a maculopapular rash that spreads from the trunk to the extremities.
  — Gastrointestinal involvement is possible, and more common in children.
  — Cases are typically mild, but severe cases can lead to renal dysfunction or respiratory impairment (experienced as cough, dyspnea).
  — Small mammals, particularly cats and rodents, are key reservoirs; their fleas are the vectors.

Orientia tsutsugamushi

• Scrub fever
  — Fever, intense headahces, mylagias, and a maculopapular rash that starts on the trunk; in some cases, eschars will form, especially at the site of inoculation.
  — Lymphadenopathy and pulmonary and neurologic involvement are common; gastrointestinal involvement may also occur.
  — Reservoirs include mites (chiggers) and rodents; mites are the vector.

Ehrlichia chaffeensis

• Human monocytic ehrlichiosis
  — Fever, headache, and myalgia; Coughing is common in adults.
  — The rash associated with this infection varies, and is more common in children.
  — Central nervous system involvement is possible.
  — Leukopenia, thrombocytopenia, and elevated transanimases.
  — Deer, dogs, and other mammals are common reservoirs; soft ticks are the vector.

Anaplasma phagocytophilum

• Granulocytic anaplasmosis
  — Similar symptoms and signs to human monocytic ehrlichiosis
  — Rash is rare.
  — Small mammals are the reservoirs; soft ticks are the vector.

Coxiella burnettii

• Q fever
  — Fever, headache, and myalgia, but no rash.
  — Chronic Q fever can lead to serious complications, including hepatitis, pneumonia, and subacute endocarditis.
  — Reservoirs include mammals, ticks, and birds; though ticks are a potential vector, most cases of Q fever are the result of the aerosol inhalation or consumption of the bacteria in contaminated milk.