against the sclera in episcleritis and is displaced forward in scleritis.

4.1.5Associated Diseases

Connective tissue diseases, herpes zoster, rosacea, gout, syphilis, and atopy are the diseases most commonly associated with episcleritis [2, 5, 17]. Twenty-seven percent of our patients with episcleritis had an associated disease (Table 4.2), including 15% (13 patients) with a connective tissue disease or a vasculitic disease, 6% (5 patients) with infectious diseases, 5% (4 patients) with rosacea, and 1% (1 patient) with atopy (Table 4.3). No associated diseases were found in the remaining patients.

Although gout and syphillis have been considered to be possible causes of episcleritis, the reported incidence varies between 0% [17] and 7% [3] for gout and between 0% [18] and 3% [3] for syphilis. No cases of gout or syphilis were detected in our series. Erythema nodosum is considered a hypersensitivity reaction to a variety of antigenic stimuli, and thus may be seen in the course of several diseases of both known and idiopathic cause, some of which also can be associated with episcleritis: bacterial (streptococcal), mycobacterial (tuberculosis), and chlamydial (psitaccosis) infections, sarcoidosis, arthritis associated with inßammatory bowel disease, and Beh•etÕs disease. However, erythema nodosum may occur without any identiÞable systemic illness [22, 23]. Episcleritis can appear at the same time as the painful subcutaneous nodules of erythema nodosum appear on the legs and usually resolves as the nodules disappear [3, 18, 24, 25]. Because erythema nodosum is a sign of other potential underlying diseases, whether identiÞable or not, we have not considered it as a separate diagnostic entity. Two of our patients with episcleritis had erythema nodosum; in neither of them was a speciÞc associated disease found. Although some patients with episcleritis give a past history of rheumatic heart disease, the conditions have not been described as occurring at the same time [3]. Two of our

patients with episcleritis had had rheumatic fever in the past; however, we did not consider the conditions associated because they had not been concomitant.

4.1.6Precipitating Factors

There are several factors that have been described as putative triggers of recurrent episcleritis, but the reports come from sporadic anecdotes without any statistical basis. Emotional stress has been related to recurrent attacks, as in the case of the physician who had episodes of active episcleritis associated with the medical board examination, professional paper presentations, and job interviews [26]. In many instances, our patients experienced the onset of some recurrent attacks during stressful life periods. The inßuence of emotions on physical illness has also been described for ulcerative colitis, systemic lupus erythematosus, and various forms of cutaneous diseases (dyshidrosis, alopecia areata, and neurodermatitis) [27Ð31]. Studies designed to investigate the relationship between stress and inßammation do not allow any deÞnitive conclusion (indeed, design and execution of such studies are difÞcult because of the variables involved and the subjective nature of the data), but insights gained from the emerging embryonic Þeld of neuroimmunology lend scientiÞc support to such a relationship. Various neurochemicals released during various emotional states, such as anger, anxiety, and depression, affect various types and subtypes of white blood cells through speciÞc cell surface receptors [32]. It is even possible, through operant conditioning techniques, to develop in experimental animals a state of immunosuppression in response to a nonimmunosuppressive stimulus [33].

Menstruation and/or ovulation also has been associated with recurrent attacks [34Ð38], as in the case of a woman who, for 5 years, regularly had episodes of active episcleritis a few days prior to her menstrual period [36], or as in the case of another woman who, for 7 years, had recurrent episcleritis during her ovulation period [38].