Atopic conditions in search of pathogenesis and therapy.

Allergy and asthma have reached epidemic proportions, with almost 20% of Americans affected, and both have been associated with obesity and stress, which are prominent in our society. Moreover, there has been an emergence or ecognition of a number of additional conditions that share many symptoms traitionally associated with classic allergic diseases. These conditions are quite disinct in that such patients are not typically allergic in the usual sense of having ositive radioallergosorbent test and skin prick test results to known antigens. Such conditions include mast cell activation syndrome (MCAS), coronary hypersensitivity (Kounis) syndrome, multiple chemical sensitivity (MCS) syndrome, gluten intolerance without celiac disease, food intolerance associated with attention-deficit/hypersensitivity disorder, and autism. Additional conditions include cyclic vomiting syndrome, cystitis/bladder pain syndrome (IC/BPS), myalgic encephalopathy or chronic fatigue syndrome (CFS), and fibromyalgia syndrome (FMS). Most patients with MCAS present with abdominal pain or diarrhea, skin reactions and flushing, and headaches or memory and concentration difficulties (brain fog) associated with activation of the unique tissue immune cell, the mast cell (MC). MCAS should be suspected when there is unexplained multiorgan involvement in the absence of elevated serum tryptase levels. In Kounis syndrome, patients experience sudden unexplained coronary events, often immediately after some hypersensitivity reaction, suspected to activate intracoronary MC to release proinflammatory mediators. The MCS syndrome is a chronic condition characterized by not only nausea, fatigue, dizziness, and headaches but also inflammation of skin, joints, gastrointestinal tract, and airways, often resembling MCAS. These symptoms develop when patients are exposed to triggers that include smoke, pesticides, plastics, synthetic fabrics, scented products, and paints. Autism is a neurodevelopmental disorder characterized by impaired social interactions, language loss, and repetitive behaviors. It is often precipitated after some infectious or stress trigger and can be associated with gastrointestinal and skin reactions. Cyclic vomiting syndrome is a gastrointestinal disorder seen primarily in children, characterized by bouts of unexplained vomiting, often precipitated by stress that may overlap with MCS syndrome. IC or PBS is defined as low pelvic pain or pressure associated with increased daytime frequency of urination and nocturia for more than 3 months in the absence of a urinary tract infection. Chronic prostatitis in men seems to be a similar condition, and the 2 together are now called urologic pelvic pain syndrome. They are often comorbid with CFS and FMS. CFS is characterized by debilitating fatigue lasting longer than 6 months that is not relieved with rest, as well as at least 4 of the following: malaise after intense exercise, unrefreshing sleep, impaired memory or concentration (brain fog), muscle pain, polyarthralgia, tender lymph nodes, and new headaches. It is often comorbid with MCAS and FMS. Patients with FMS present with long-term, body-wide pain and tenderness in the joints, muscles, tendons, and other soft tissues, typically reflected by sets of 9 painful tender or trigger points along the back. In addition, FMS is associated with fatigue, sleep disturbances, headaches, depression, and anxiety. All these conditions involve sterile inflammation and worsen with stress, but the pathogenesis is unknown, thus hampering the development of effective treatments. A possible common link appears to be the MC (Figure 1). For this eason, the Mastocytosis Society, with support from the American Academy of Allergy, Asthma, and Immunology, reated a DVD to highlight MC involvement not only in allergy but also in many other conditions (Figure 2). It is interesting that Hans Selye first wrote The Stress of Life in 1956 and then wrote a book entitled The Mast Cell in Theoharis C. Theoharides, MS, PhD, MD