Chapter 19: Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP), also referred to as extrinsic allergic alveolitis, is characterized by non-IgE-mediated inflammation of the parenchyma, alveoli, and terminal airways of the lung initiated by inhaled antigens in a susceptible host. Etiologic agents of HP are either organic high molecular weight compounds such as bacteria, fungi, amoebae, plant, and animal proteins or inorganic low molecular weight haptens such as isocyanate and drugs including amiodarone, nitrofurantoin, and minocycline. Six significant predictors have been identified that provide ∼95% diagnostic accuracy. These six predictors are (1) exposure to a known offending allergen, (2) positive precipitating antibodies to the offending antigen, (3) recurrent episodes of symptoms, (4) inspiratory crackles on lung auscultation, (5) symptoms occurring 4-8 hours after exposure, and (6) weight loss. HP is staged into acute, subacute, and chronic. In the acute stage after direct exposure to the antigen, there is fever, chills, nonproductive cough, dyspnea, malaise, and myalgias, all resembling influenza. However, if obtained, a chest radiograph shows nodular infiltrates, and pulmonary function testing is restrictive (unless the cause is avian in which obstruction or obstruction with restriction is present). In the chronic stage, fever and chills are absent, but weight loss can occur. The immunologic response includes activated macrophages and CD8(+) cytotoxic lymphocytes, and bronchoalveolar lavage fluid reveals marked lymphocytosis with a ratio of CD4(+) cells to CD8(+) cells <1. Activated macrophages have increased expression of CD80/CD86, and T cells have increased expression of its counter-ligand CD28, evidence for heightened antigen presentation.

Chapter 25: Idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) is defined as anaphylaxis without any identifiable precipitating agent or event. The clinical manifestations of IA are the same as allergen-associated (immunologic) anaphylaxis and include urticaria, angioedema, hypotension, tachycardia, wheezing, stridor, pruritus, nausea, vomiting, flushing, diarrhea, dysphagia, light-headedness, and loss of consciousness. Patients usually tend to have the same manifestations on repeated episodes. IA is a prednisone-responsive disease that is ultimately a diagnosis of exclusion. Approximately 40% of patients are atopic. Serum tryptase (or urine histamine or its metabolite) will be elevated acutely but if elevated in the absence of anaphylaxis, should suggest alternative diagnoses including indolent systemic mastocytosis. A focused history, examination, and follow-up will dictate whether a patient's symptoms may be attributable to disorders that mimic anaphylaxis, such as indolent systemic mastocytosis, carcinoid syndrome, pheochromocytoma, hereditary angioedema acquired C1 esterase inhibitor deficiency, or panic attacks. The presence of urticaria may help limit the differential because they do not usually accompany any of the aforementioned disorders, except for indolent systemic mastocytosis. IA is classified according to the symptoms as well as the frequency of attacks. Patients who experience six or more episodes in a year or two or more episodes in 2 months are classified as IA-frequent (IA-F). Patients who experience fewer episodes are classified as IA-infrequent (IA-I). This distinction is important because IA-F patients initially will require prednisone as disease-modifying therapy whereas most IA-I patients will not. Patients with IA must carry and know when and how to self-administer epinephrine.

Chapter 26: Eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is distinguished from gastroesophageal reflux disease (GERD) by persistent esophageal eosinophilia despite medical therapy with proton-pump inhibitors for 4-6 weeks. In children, symptoms vary by age groups such as feeding disorders in 2 year olds; vomiting in 8 year olds; and abdominal pain, dysphagia, and/or food impaction in adolescents. Most adults present with dysphagia, food impaction, heartburn or chest pain. Common endoscopic features in adults with EoE include linear furrows (creases that orient longitudinally), mucosal rings (esophageal "trachealization"), small-caliber esophagus, white plaques or exudates (which are microabscesses of eosinophils), and strictures. Children often present with similar endoscopic features, but one-third of pediatric patients with EoE have normal endoscopy. Histological features of EoE include increased intramucosal eosinophils in the esophagus (≥15 eosinophils/high-power field) without similar findings in the stomach or duodenum. There also may be eosinophilic microabscesses. In addition to evidence of mast cell activation, mucosa from patients with EoE have increased IL-5, supporting eosinophilia, and up-regulation of gene expression of eotaxin-3, a chemokine important in eosinophil migration. The majority of patients have evidence of either aeroallergen and/or food sensitization. An elemental/amino acid-based formula diet has shown to be effective in children but may not be well tolerated by adults because of taste and volume or high expense. Topical corticosteroids improve esophageal eosinophilia and symptoms and have become the "gold standard" of pharmacotherapy.