Subcutaneous mycosesmycotic infection of the subcutaneous tissues, the dematiaceous (brown-pigmented), develops rounded sclerotic bodies. Infections are caused by the traumatic implantation of fungal elements into the skin and are chronic, slowly progressive and localized. Tissue proliferation usually occurs around the area of inoculation producing crusted, verrucose, wart-like lesions. World-wide distribution but more common in bare footed populations living in tropical regions.

A- Chromoblastomycosis Refers to chronic infections caused by brownwalled, round, nonbudding, dematiaceous fungi (sclerotic or copper penny bodies) Is a fungal infection of the skin and subcutaneous tissue. It can be caused by many different types of fungi which become implanted under the skin, often by thorns or splinters. Chromoblastomycosis spreads very slowly; it is rarely fatal but it can be very difficult to cure. producing either plaque-like, or nodular, verrucous, crusted, ulcerated, and dense dermal fibrotic lesions (may be on pedicles and resembling cauliflowers). The lesions occur on any part of the body, but usually on the arms, legs, face, or trunk. If untreated, lesions slowly spread over large areas. The etiologic agents of chromoblastomycosis are generally members of three genera of fungi that inhabit the soil:

I. Fonsecaea sp.: Produces septate, dark brown hyphae, conidia are brown and barrel-shaped.

II.Phialophora sp.: The conidiophores are short; their conidia are unicellular and produced from a flask shaped phialide.

III. Cladosporium sp.: live-green to brown or black colonies, and have darkpigmented conidia that are formed in simple or branching chains.

Pathogenicity:Seventy to 90% of cases are caused by Fonsecaea pedrosoi. Sporadic cases have been caused by other melanized molds. Melanin in the cell wall, secreted proteinase, wall associated phosphatase; conversion to muriform

cells that are resistant to lysis. Calcium ions and the micronutrient Mn+2 is implicated in form development of muriform cells.

Fonsecaea sp Phialophora sp.

Cladosporium sp

B- Phaeohyphomycosis

Is the infections caused by dematiaceous (pigmented) filamentous fungi which contain melanin in their cell walls. Phaeohyphomycosis is an uncommon infection, but it has been increasing in recent years.It is also seen that many patients with subcutaneous and systemic pheohyphomycosis have underlying immunodeficiency in contrast to chromoblastomycosis patients who are generally in good health.

Causative agents: .Alternaria sp., Aureobasidium pullulans, Bipolaris sp., Cladophialophora bantiana,  Curvularia sp., Exophiala sp.,  Phialophora verrucosa. 

Note: Direct microscopy of tissue is necessary to differentiate between chromoblastomycosis which is characterized by the presence in tissue of brown pigmented, planate-dividing, rounded sclerotic bodies and phaeohyphomycosis where the tissue morphology of the causative organism is mycelial.

Laboratory Diagnosis:

1. Direct Microscopy: a. Skin scrapings should be examined using 10% KOH and Parker ink or calcofluor white mounts

2. Culture: Clinical specimens should be inoculated on Sabouraud's dextrose agar. The mold forms grow as a gray “mouse fur” colony with a black reverse. Microscopically each species has different asexual reproductive structures, all containing brown pigment, the arrangement of conidia, slide culture preparations are recommended.  Culture identification is the only reliable means of distinguishing these fungi.

3.Histopathology:

Tissue sections should be stained using H&E. The tissue form of all causative species consists of golden-brown round cells: muriform cells, also known as sclerotic bodies, or “copper pennies.” These divide by internal cleavage planes not by budding.

4. Serology: There are currently no commercially available serological test for the diagnosis of chromoblastomycosis.

Treatment: is difficult and prolonged. It may include:Antifungals: larger lesions are difficult to treat itraconazole or posaconazole (ITC) and/or terbinafine (TRB), for periods of 6 – 12 months or more.

Cryotherapy (is a standard treatment for warts and can be done in a doctor's office. The liquid nitrogen application usually takes less than a minute)

Surgery Small lesions surgery to remove the affected tissue completely.

C- Sporotrichosis a chronic mycotic infection of the subcutaneous tissues and adjacent lymphatics characterized by nodular lesions which may suppurate and

ulcerate. Infections are caused by the traumatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs. Secondary spread to articular surfaces, bone and muscle is not infrequent and the infection may also occasionally involve the central nervous system, lungs or genitourinary tract. Because the fungus is naturally found in soil, hay and plants, it usually affects farmers, gardeners, and agricultural workers. It enters through small cuts in the skin to cause the infection, it progresses slowly. The first symptoms may appear 1 to 12 weeks after the initial exposure to the fungus. Serious complications can also develop in immune compromised patients.

Epidemiology Sporotrichosis occurs worldwide mainly in warm and humid regions of the tropical and subtropical countries. Most frequent occurrence is in Japan, China, Indiae disease frequently occurs in young individuals between 20 and 50 years of age.

Sporothrix schenckii e causative fungus is a dimorphic yeast. Produces septate hyaline hyphae. Conidia have two types. The first type is unicellular, hyaline to brown, oval, thin-walled, and are typically arranged in rosette-like clusters at the tips of the conidiophores.

The second type of conidia are brown, oval or triangular, thick-walled, sessile attached directly to the sides of the hyphae.

Clinical manifestations: Fixed cutaneous sporotrichosis: Primary lesions develop at the site of implantation of the fungus, usually at more exposed sites mainly the limbs, hands and fingers. Lesions often start out as a painless nodule which soon become palpable and ulcerate often discharging purulent fluid. Importantly, isolates from these lesions grow well at 35oC, but not at 37oC.

Lymphocutaneous sporotrichosis: Primary lesions develop at the site of implantation of the fungus, but secondary lesions also appear along the lymphangitic channels, they start out

as painless nodules which soon become palpable and ulcerate. Isolates from these lesions usually grow well at both 35oC and 37oC.

Sporothrix schenckii

Pulmonary sporotrichosis: .This is a rare entity usually caused by the inhalation of conidia but cases of haematogenous dissemination have been reported. Symptoms are nonspecific and include cough, sputum production, fever, weight loss and upper-lobe lesion. Haemoptysis may occur and it can be massive and fatal.

Osteoarticular sporotrichosis: .Most patients also have cutaneous lesions and present with stiffness and pain in a large joint, usually the knee, elbow, ankle or wrist. Osteomyelitis seldom occurs without arthritis.

Laboratory diagnosis: 1. Clinical material: Specimens most commonly collected for identificationare aspirated pus, scrapings, or biopsied tissue from cutaneous or subcutaneous lesions.

2. Direct Microscopy: Tissue sections should be stained using PAS digest or Gram stain. Swabs taken from open lesions and placed in sterile normal salineovernight at 37◦C to produce large numbers of characteristic yeast cells, which appears as elongated, “cigar” shaped to the oval.

3.Culture: S. schenckii grows well as a mold on SDA (with antibiotics but without cycloheximide) and held at 25–30◦C for up to 4 weeks with characteristic “daisy cluster” sporulation and melanized sessile conidia.

Confirmation of the fungus requires conversion to the yeast form on BA or BHI– Brain heart infusion agar supplemented with 5% sheep blood agar at 37◦C. Growth at 35–37◦C is an important for pathogenicity. Yeast colonies may appear wrinkled and an off-white, cream color.

4.Serology: Serological tests are of limited value in the diagnosis of Sporotrichosis.

Molecular Diagnosis The detection of S. schenckii by polymerase chain reaction (PCR) is useful in diagnosing extracutaneous and disseminated forms.

Treatment:First-line therapy consists of ITC (itraconazole) capsule at a dosage of 100–200 mg/day (oral) until 2–4 weeks after all lesions have resolved, for 3–6 months

Second-Line Therapywhen ITC therapy fails, A saturated solution of potassium iodide (SSKI), taken orally, was the standard treatment for many years, even though the mechanism of action remains unknown. SSKI treatment is initiated with 5 drops 3×/day (with a standard eyedropper) usually added to water, fruit juice, or milk before drinking. The dosage is increased gradually until 40–60 drops 3×/day is reached.