Blastomyces dermatitidis

Post By: Anil Pokhrel

1. INTRODUCTION

Blastomyces dermatitidis is a thermally dimorphic fungi originally isolated from cutaneous lesions. The teleomorph of Blastomyces dermatitidis is referred to as Ajellomyces dermatitidis. At 25⁰C-30⁰C, Blastomyces grows as a mold form with conidia and septate hyphae usually within 14 days; some strain grow more slowly. Mould form produce abundant conidia from aerial hyphae and lateral conidiophores. These conidia are spherical, ovoid, pyriform measuring 2-10 µm in diameter, resembling the macroconidia of Histoplasma capsulatum, the conidia of Blastomyces are smooth. Thick walled chlamydospores 7-18 µm in diameter also may be observed in Blastomyces dermatitidis.

B. dermatitidis reproduces in tissues by budding and the typical bud is characterized by its large size, attachment to the parent cell by a persistent wall. The persistence of the bud attachment and the tendency of the parent cell to continue budding often results in a small clusters of cells with an additional bud arising from the parent cell, near the point of attachment of the first bud. Multiple budding therefore, is found in Blastomyces dermatitidis. The cells of B. dermatitidis are multinucleate, but those of H. capsulatum and Cryptococcus neoformans are uninucleate.

1.1 Cultural characteristics

The yeast-like forn of growth can be maintained in vitro by incubation on an enriched medium such as blood agar or even on Sabouraud’s agar at a temperature of 37⁰C.

On Sabouraud’s agar and other similar suitable media, at 25⁰C-30⁰C, B. dermatitidis grows as a white mold. Some strain grow slowly, do not spread widely over the agar surface and sporulate sparsely, other strains spread more widely reaching a colony diameter of 5-6 cm in 2 weeks, present a powdery or granular surface and sporulate freely. Some strains become brown or produce a diffusible dark pigment.

Conidia are smooth walled, spherical or oval, measuring 2-10 µm. They are borne on lateral, slender or cylindrical conidiophores or terminally on hyphal branches.

On enriched media at 37⁰C, B. dermatitidis grows as yeast with colonies that are folded, pasty and moist. Yeast in vitro is thick walled and spherical, they produce single bud with a characteridtically broad base of attachment between the bud and the parent cell.

2. EPIDEMIOLOGY

Benign respiratory clinical forms of blastomycosis may occur, but their frequent occurrence has not yet been proved. Mild self-limited illness have not been diagnosed, and the evidence one might expect from intradermal testing in survey studies is obscured in occurrence without evidence of transmission to the patient’s associates.

2.1 Differential incidence

Blastomyces infection occurs at all ages with slightly higher incidence in 30s-50s of ages. It is seen in male more frequent than females. No association with specific occupational exposure is recognized.

2.2 Geographical distribution

This mycosis occurs mostly in the North America in particularly in St. Lawrence Ohio and Mississippi river valley and in Africa but are not limited to these area, is also reported from some part of Asia.

 2.3 Source of infection

Blastomycosis is relatively common in dog and rarely other animals in endemic area(Jawetz). Humans are infected by inhalation of conidia from colonies of mold growing as saprobe in soil or a similar substrate; however, a few of many attempt to isolate B. dermatitidis from soil have been successful, and these have not revealed a consistent pattern of distribution or a characteristic ecological association.

3. PATHOGENESIS

The conidia of B. dermatitidis are inhaled into the lungs, where the organisms transform into yeast phase. The yeast is phagocytosed by macrophage and neutrophils (Chester’s).

The fungus initially multiplies in lung and cause pneumonia like symptoms; however, the hallmark of blastomycosis is the development of skin lesions, which arise due to hematogenous spread. Cell mediated immunity plays an important role in eradication of agent but neutrophils also play role in containing organisms. The histopathological change reflects the granulomatous and pyogenic response. Yeast cell can remain viable within granuloma for years and can be source of reactivation later on.

4. CLINICAL MANIFESTATION

4.1 Blastomycosis: Definition

Blastomycosis is a chronic granulomatous and suppurative disease which originates as a respiratory infection and disseminates, usually with pulmonary, osseus and cuataneous involvement.

It’s also called as Gilchrist’s disease.

4.2 Clinical Types of Blastomycosis

i) Pulmonary Blastomycosis

Pulmonary blastomycosis usually begins as a mild respiratory infection which progress with dry cough, pleuritic pain, hoarseness and low grade fever. Within weeks or months, sputum increases and becomes purulent and blood-streaked and there is increased temperature elevation, dyspnea and loss of weight, night sweating. The disease if untreated usually disseminates and often progress to death.

ii) Disseminated Blastomycosis

When disseminated, disease is manisfested in skin, oro-nasal mucosa and subcutaneous tissues, respiratory tract, urogenital tract, osseus system and CNS. In contrast to paracoccidiodomycosis, GI tract is rarely involved. Bone lesions are manifested by pain, osteomyelitis and peritonitis. Destructive lesions of vertebrae, tibia and femur are frequent. Compression of spinal cord may result from vertebral mycosis; in addition, meningitis and brain abscess may occur. Granuloma and abscess of liver and spleen are rarely found. The commonest site of involvement of the urogenital system are the prostate, epididymis and testis, characterized by dysuria, pyuria and hematuria.

iii) Cutaneous Blastomycosis

Cutaneous blastomycosis may originate as a subcutaneous nodule or as a papule or as postule which ulcerates. A cutaneous lesion may develop as an ulcer on an exposed skin surface at the site of injury. Even though,, most cutaneous lesions are the result of hematogenous spread from a pulmonary or other visceral organs lesion to cutaneous site, the possibility that such is the result of local implantation cannot be ruled out. The cutaneous lesions develops within weeks or months into ulcerated or verrucous granuloma with an advancing border elevated to 1-3 mm with abruptly sloping outer border. The central area of the lesion may be verrucous or ulcerated and covered with the crust.

Base of lesion is granulomatous and the elevated border is indurated, dusky, red or violaceous. Characteristic budding cells of B. dermatitidis can be demonstrated in the pus from these abscess. Lesion slowly spreads over the face, often deforming the features and leaving scar over central area of old lesions.

5. LABORATORY DIAGNOSIS

5.1 Specimens

Sputum, bronchoalveolar lavage, tracheal aspirates, lung biopsy, blood, bone marrow, lesions of mucocutaneous abscess.

5.2 Diagnostic Procedures

i) Direct Microscopy

Specimens such as concentrated sputum, pus, etc. can be examined directly after treating with KOH or calcoflour white or both for visualization of yeast.

ii) Histopathology

Histopathological examination of tissue specimens obtained from biopsy by H and E , PAS, GMS, Giemsa or wright staining technique for pathological change and to demonstrate fungus.

iii) Culture

Specimen is inoculated on Sabouraud’s agar slant and incubated at 25⁰C-30⁰C for mold from isolation, if bacterial contaminants are suspected media can be incorporated with antibiotics such as penicillin, streptomycin or chloramphenicol and for contaminating saprophytic fungi, cylcoheximide can be used.

For isolation of Yeast form specimen can be inoculated into glucose blood agar and incubated at 37⁰C.

Normally sterile specimen such as CSF may be directly inoculated into blood agar, BHI agar/ broth, SGA, etc.

B. dermatitidis grows rather slowly and cultures should be held for a month before they are discarded as negative.

iv) Exoantigen Detection

The exoantigen detection technique is a simple diagnostic method that detects the presence of cell free antigens, known as exoantigen, which are produced by the mycelial form cultures.

A specific exoantigen detected in the aqueous extract of a mycelial culture may identify any of systematic dimorphic fungi.

v) Nucleic Acid Probes

The use of nucleic acid probe is an important advancement in the identification of dimorphic fungi from cultures. Probes for the identification of B. dermatitis, H. capsulatum and Cryptococcus immitis are commercially available. 

6. IDENTIFICATION

Direct calcoflour white or KOH mount of sputum exudates and tissues can demonstrate the yeast of B. dermatitidis,which are large, spherical and thick walled and measures approximately 8-15 µm in diameter. The yeast cells bud singly and have a wide base of attachment between bud and parent cell. The bud of B. dermatitidis attains the same size as the parent yeast before becoming detached.

When specimen are cultured at 25⁰C-30⁰C, B. dermatitidis initially produces a fluffy, white colonies on routine mycological media. Some strains develop tan, glabrous colonies without conidia, and others may produce light brown colonies with concentric rings. 2-10 µm conidia measuring 2-10 µm in diameter are produced in short or long terminal or lateral hyphal branches. Conidia are typically spherical, ovoid, or pyriform. Thick-walled chlamydospores 7-18 µm in diameter also may be observed in old cultures.

At 37⁰C, yeast from grows as a white or light brown, wrinkled colony, in vitro or in tissue, yeast are thick walled and spherical; they produce single bud with a characteristically wide base of attachment between parent cell and bud but bud with narrow attachment may also be seen.

7. TREATMENT

Severe case of blastomycosis is treated with amphotericin B. In patients with confirmed lesions are treated with 6 months course of itraconazole. 

REFERENCES 

1.  Wolsh TJ, Larone DH, Schell WA and Mitchell TG (2003). Histoplasma, Blastomyces, Coccidiodiodes and other Dimorphic Fungi causing systemic mycoses in Murray PR (ed. In chief). Manual of Clinical Microbiology. 8^th Edition. 2^nd Vol. ASM Press, Washington. Pp 1781-1794

2.    Emmons CW, Binford CH, Utz JP and Kwon-Chung KJ (1977). Medical Mycology. 3^rd ed. Lea and Febiger Philadelphia. Pp 342-363 

3.   Corroll KC, Morse SA, Meitzner T and Miller S (2013). Jawetz Melnick and Adelberg’s Medical Microbiology. 27^th ed. Mc Graw Hill, Lange. Pp 681-682 

4. Kauffman CA (2007). Endemic Mycosis, in Engleberg NC, DiRito V and Dermody TS. Schaechter’s Mechanism of Microbial Disease. 4^th ed. Lippincott Williams and Wilkins, Philadelphia. Pp 455-462