Alpha 1-antitrypsin deficiency was documented in one case, interferon-alpha therapy in another case. Similar cases of granulomatous mastitis were reported in IgG4-related disease though the exact relationship to IGM remains to be elucidated. Other contributing factors of IGM were investigated such as oral contraceptives usage. Many cases were reported after use of prolactin elevating medications such as antipsychotics.Elevated prolactin levels have the direct effects of increasing secretory activity of breast lobules, maintaining tight junctions of the ductal epithelium, preventing involution of the breast gland after weaning and are known to stimulate the immune system, contributing to both physiological and pathological granulomatous lesions and non-caseating granulomas. PRL is also secreted locally in the breast and local secretion by lymphocytes may be enhanced during inflammatory reactions. Autoimmune reaction to extravasated fat and protein rich luminal fluid (denaturized milk) resulting from the secretory activity is assumed to be one of the triggers of IGM. Several other hormones can contribute to PRL signaling in the breast gland, high levels of insulin caused for example by peripheral insulin resistance (resulting from pregnancy, gestational diabetes or developing diabetes mellitus type 2) will enhance the galactogenic and antiapoptotic effects of PRL and growth hormone by acting synergistically with IGF-1. Microbiology
The presence of Corynebacterium in granulomatous mastitis was first reported in 1996. Since then multiple reports have confirmed the presence of this genus in granulomatous mastitis. The most commonly isolated species is Corynebacterium kroppenstedtii. A selective medium for the isolation of this species has been described.
Chemistry
Zileuton is an active oral inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes, 5-hydroxyeicosatetraenoic acid, and 5-oxo-eicosatetraenoic acid from arachidonic acid. The chemical name of zileuton is (±)-1-(1-Benzo[b]thien-2-ylethyl)-l-hydroxyurea.The molecular formula of zileuton is C11H12N2O2S with a molecular weight of 236.29. The formulation from the manufacturer is a racemic mixture of R(+) and S(-) enantiomers. Pharmacokinetics
Following oral administration zileuton is rapidly absorbed with a mean time to peak blood serum concentration of 1.7 hours and an average half-life elimination of 2.5 hours. Blood plasma concentrations are proportional to dose, whereas the absolute bioavailability is unknown. The apparent volume of distribution of zileuton is approximately 1.2 L/kg. Zileuton is 93% bound to plasma proteins, primarily to albumin, with minor binding to alpha-1-acid glycoprotein. Elimination of zileuton is primarily through metabolites in the urine (~95%) with the feces accounting for the next largest amount (~2%). The drug is metabolized by the cytochrome P450 enzymes: CYP1A2, 2C9, and 3A4. Adverse effects
The most common adverse reactions reported by patients treated with Zyflo CR were sinusitis (6.5%), nausea (5%), and pharyngolaryngeal pain (5%) vs. placebo, 4%, 1.5%, and 4% respectively. Interactions
Drug interactions
Zileuton is a minor substrate of CYP1A2, 2C8/9, 3A4, and a weak inhibitor of CYP 1A2. The drug has been shown to increase the serum concentration or effects of theophylline, propranolol, and warfarin, although significant increase in prothrombin time is not obvious. It is advised that the doses of each medication be monitored and/or reduced accordingly.