Q:

I have 3 questions. I do appreciate your time and you for answering all my questions!

 

If a patient has been taking prednisone 5-10 mg daily (and 3-4 times a year a short burst) for more than 20 years, can that affect responses to allergen skin testing?

 

What are the most common fungi involved in allergic fungal sinusitis and bronchopulmonary disease (besides Aspergillus fumigatus)?

 

Is there any list of cephalosporins with similar/cross reacting side chains? Thank you again.

A:

Thank you for your recent inquiry.

I will try and answer your questions, as best I can, in the order you asked them.

Unfortunately I cannot give you a definitive answer to your question regarding the effects of long-term prednisone administration. There are simply no data on the effect of long-term administration of prednisone on the allergy skin test. In addition, we have no significant dose ranging data in this regard. The best I can do is point you to a response already posted on our website. It was posted on 12/23/10, and entitled "Effect of prednisone on allergy skin tests." You can access this response by typing "prednisone, skin test" in the search box on the Academy's Ask the Expert website.

The causative agents most commonly associated with allergic fungal sinusitis are the dematiaceous fungi. They consist of the genre Helminthosporium, Fusarium, Alternaria, Drechslera, Curvularia, Exserohilum, and Bipolaris. The first cases described were to Aspergillus. However, Aspergillus-associated allergic fungal sinusitis only accounts for a small percentage of the cases. Adults have a greater incidence of Aspergillus-induced disease than do children (1).

However, these general observations may vary geographically. In India (see abstract copied below), Aspergillus seems to account for the majority of cases of allergic fungal sinusitis.

Allergic bronchopulmonary disease has also been associated with fungi other than Aspergillus. However, Aspergillus seems to be far more predominant as a cause of allergic bronchopulmonary disease than do other fungi. Allergic bronchopulmonary mycoses has been associated with Curvularia, Candida, Fusarium, Penicillium, Drechslera, Stemphyllium, Pseudallescheria, and Helminthosporium.

In addition, a number of Aspergillus species other than Aspergillus fumigatus have caused allergic bronchopulmonary mycoses. These include the following: Aspergillus nidulans, Aspergillus terreus, Aspergillus glaucus, Aspergillus niger, and Aspergillus flavus (2, 3).

The issue of cephalosporin cross-reactivity is complex and much is left unanswered. However, there are some principles of cross-reactivity that can be gleaned from a review of the most recent Update of the Practice Parameters for drug allergy (4).

Below you will see copied some general principles from this Parameter:

CEPHALOSPORIN
"Summary Statement 93: Most hypersensitivity reactions to cephalosporins are probably directed at the R-group side chains rather than the core -lactam portion of the molecule. (D)

Summary Statement 94: Skin testing with native cephalosporins is not standardized, but a positive skin test result using a nonirritating concentration suggests the presence of drug specific IgE antibodies. (D) A negative skin test result does not rule out an allergy because the negative predictive value is unknown. (D)

Summary Statement 95: Patients with a history of an immediate-type reaction to 1 cephalosporin should avoid cephalosporins with similar R-group side chains. (D) Treatment with cephalosporins with dissimilar side chains may be considered, but the first dose should be given via graded challenge or induction of drug tolerance, depending on the severity of the previous reaction. (D)"

In specific answer to your question, the cephalosporins that share similar R groups are found in this recent Parameter (Reference 4). You should be able to access this document free of charge. It is present on the Joint Council of Allergy, Asthma, and Immunology website and has also, as you can see from the reference, been published in the Annals of Allergy, Asthma, and Immunology. Tables 16 and 17, which are found on Pages 273 e49 and 273 e48, list beta lactam antibiotics according to shared side chains of both the R1-group side chain as well as the R2-group side chain. In addition, there is a discussion of the significance of side chain reactions for beta lactams as a whole on these two tables. I tried to copy and paste them for your convenience in this response, but they did not align properly when I attempted to do so. Nonetheless, you should be able to access the Parameter without any difficulty.

Thank you again for your inquiry and we hope this response is helpful to you.

Indian J Pathol Microbiol. 2008 Oct-Dec;51(4):493-6.
Mycological profile of fungal sinusitis: An audit of specimens over a 7-year period in a tertiary care hospital in Tamil Nadu.
Michael RC, Michael JS, Ashbee RH, Mathews MS.
Source
Department of Microbiology, Christian Medical College and Hospital, Vellore 632 004, Tamil Nadu, India.
Abstract
Background: Fungi are being increasingly implicated in the etiopathology of rhinosinusitis. Fungal sinusitis is frequently seen in diabetic or immunocompromised patients, although it has also been reported in immunocompetent individuals. Invasive fungal sinusitis, unless diagnosed early and treated aggressively, has a high mortality rate.
Aim: Our aim was to look at the mycological and clinical aspects of fungal sinusitis in a tertiary referral center in Tamil Nadu.
Design: This is a retrospective audit conducted on fungal culture positive sinus samples submitted to the Microbiology department from January 2000 to August 2007. Relevant clinical and histopathological details were analysed.
Results: A total of 211 culture-positive fungal sinusitis samples were analysed. Of these, 63% had allergic fungal sinusitis and 34% had invasive fungal sinusitis. Aspergillus flavus was the most common causative agent of allergic fungal sinusitis and Rhizopus arrhizus was the most common causative agent of acute invasive sinusitis. A significant proportion of these patients did not have any known predisposing factors.
Conclusion: In our study, the etiology of fungal sinusitis was different than that of western countries. Allergic fungal sinusitis was the most common type of fungal sinusitis in our community. Aspergillus sp was the most common causative agent in both allergic and chronic invasive forms of the disease.

References:
McClay JE, et al. Clinical presentation of allergic fungal sinusitis in children. Laryngoscope 2002; 112(3):565-569.
Greenberger P. J Allergy Clin Immunol 1984; 74:645-652. \
Greenberger PA. Allergic bronchopulmonary aspergillosis. In: Allergy: Principles and Practice 2003; Volume 2, 6th edition, pages 1353-1399.
Solensky R, Khan DA, Bernstein IL, Bloomberg GR, Castells MC, Mendelson LM, Weiss ME, et al. Drug Allergy: An Updated Parameter. Ann Allergy 2010; 105:273e1 - 273e78.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology