Vol. 17, No. 17
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, April 27, 1998
A. Provided by Marguerite-Hawkins, Epidemiology and Disease Control Program, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
From April 16, 1998 through April 22, 1998, 5 outbreaks have been reported to the Maryland Department of Health and Mental Hygiene as follows:
B. The Johns Hopkins Hospital. Information provided by Dr. Frank Holmes, Dept. of Pathology.
Case Report
The patient is a 47 year-old white male with a seven year history of chronic sinusitis, nasal polyposis, and asthma. His symptoms started around the time he began a new job as a cement mixer. The patient has since undergone multiple endoscopic sinus surgeries, after which his symptoms would improve for a while but then return. He has also received multiple courses of antibiotics, oral steroids, steroid nasal sprays, as well as WaterPik irrigation without complete resolution of his symptoms. On presentation, the patient complained of persistent headaches, nasal congestion, facial pain and pressure, and copious amounts of nasal secretions, which he stated were often foul-smelling and caused him to have persistent cough. A CT scan showed diffuse mucosal thickening involving both maxillary sinuses, along with opacification of both frontal sinuses, anterior and posterior ethmoid sinuses, and the right sphenoid sinus. A search for possible allergic fungal causes, including an immunologic panel for thermophilic Actinomyces and Aspergillus species, was negative. Furthermore, total serum IgG, IgM, IgA, and IgE were all within normal limits. Material was suctioned from his nasal cavity and sent for histology and fungal culture. The histologic material revealed numerous septated, branching, rather wide hyphal forms, some of which were brown in color, along with rare macroconidia showing transverse and longitudinal septations, in a background of mucus and inflammation, including scattered eosinophils. A Fontana-Masson stain confirmed the presence of melanin pigment, consistent with a phaeohyphomycosis. The fungal culture grew Alternaria.
Phaeohyphomycosis
Phaeohyphomycosis refers to a mycotic infection caused by dematiaceous (darkly pigmented) fungi. These infections frequently involve cutaneous and subcutaneous tissues and occasionally systemic organs, particularly the central nervous system, in immunosupressed patients. These infections range from indolent subcutaneous lesions, probably resulting from direct inoculation of fungi at the site, to devastating, destructive infections that are almost always fatal. Another distinctive clinical entity is chronic sinusitis in which the hyphae are contained within the sinuses, or, less commonly, extend through the bony walls to invade adjacent tissue. Dematiaceous fungi are also rare causes of keratomycosis involving the eye.
The diagnostic feature of phaeohyphomycosis is brown pigmentation of the hyphae due to melanin production. The color can usually be discerned in stained tissue sections but is sometimes demonstrated better in unstained sections. The production of melanin can be confirmed with a Fontana-Masson stain.
Alternaria spp.
The genus Alternaria includes A. alternata and other species. These saprophytic fungi are ubiquitous, occurring on many kinds of plants, in the soil, and on various foods. It is a common tomato pathogen. In humans, it has been described as an important cause of allergic, fungal sinusitis, along with Aspergillus and Candida. Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. A recent study looked at the effect of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency in vitro. It found a statistically significant inhibition of ciliary beat frequency after exposure to solutions from isolates of these organisms and stated that it might represent one virulence factor involved in the development of fungal sinusitis.
Alternaria has also been described as a cause of eosinophilic pneumonia and has been reported to be a major allergen associated with the development of asthma in children, especially those raised in a semiarid environment. One study in Italy looked at the prevalence of Alternaria sensitization in nearly three thousand patients suffering from respiratory symptoms. Of the 10.4% who were positive, 79.7% suffered from rhinitis and 53.3% suffered from asthma. Their conclusion was that Alternaria should be included in the immunologic panel used to investigate patients who might be suffering from a respiratory allergy.
Cutaneous infection is rare and occurs mainly in immunocompromised patients. Steroid therapy, especially systemic but also local, and Cushing's syndrome are two important predisposing factors. It is felt that cutaneous fragility induced by corticosteroids is an important cofactor in permitting direct inoculation of the fungus from the environment. Other infections caused by Alternaria include keratomycosis and onychomycosis. Invasive infections occur rarely.
Therapy
Alternaria is susceptible to amphotericin B, fluconazole, itraconazole, and ketoconazole in vitro.
Microbiology
Colonies are grown on Sabouraud-dextrose agar with and without gentamycin. The organism is inhibited by cycloheximide. Macroscopically, the colonies have a downy to woolly texture and might start as light gray in color initially but will later become dark gray. Microscopically, the organism forms septated hyphae, which are light to dark brown. The conidia are golden-brown, football-shaped with an apical beak and contain 3 to 8 transverse septa and 1 to 2 longitudinal septa. They are formed in long, branching chains of 10 or more.
References
Cody DT, McCaffrey TV, Roberts G, Kern EB. Effects of Aspergillus fumigatus and Alternaria alternata on human ciliated epithelium in vitro. Laryngoscope. 107:1511-4, 1997.
Corsico R, Cinti B, Feliziani V, et al. Prevalence of sensitization to Alternaria in allergic patients in Italy. Ann Allergy Asthma Immunol. 80:71-6, 1998.
Halonen M, Stern DA, Wright AL, et al. Alternaria as a major allergen for asthma in children raised in a desert environment. Am J Respir Crit Care Med. 155:1356-61, 1997.
Machet L, Jan V, Machet MC, et al. Cutaneous alternariosis: role of corticosteroid-induced cutaneous fragility. [Review]. Dermatology 193:342-4, 1996.
Ogawa H, Fujimura M, Amaike S, et al. Eosinophilic pneumonia caused by Alternaria alternata. Allergy. 52:1005-8, 1997.