Differential expression of leukocyte immunoglobulin-like receptors on cord-blood-derived human mast cell progenitors and mature mast cells.

The leukocyte Ig-like receptors (LILRs) comprise a family of cell-surface immunoregulatory receptors with activating and inhibitory members. The inhibitory LILRs possess cytoplasmic ITIMs that down-regulate signaling by nonreceptor tyrosine kinase cascades. The activating members have a truncated cytoplasmic domain and signal through the FcR gamma chain. We examined the expression of LILRs on human mast cells during their development in vitro. Progenitor mast cells expressed cell surface inhibitory LILRB1, -B2, -B3, and -B4 and activating LILRA1. However, although mature cord blood-derived mast cells (hMCs) had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. Culture of progenitor mast cells or hMCs with various cytokine combinations failed to retain or induce cell surface expression of the LILRs. It is interesting that hMCs expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. Our results demonstrate that LILRs are developmentally regulated in human mast cells and that LILRB5 is expressed in mast cell granules and the release of soluble LILRB5 following IgE FcR-dependent stimulation, which has potential for amplification of mast cell-dependent, inflammatory responses.

Hereditary angioedema: Safety of long-term stanozolol therapy.

BACKGROUND: Attenuated androgens control attacks of hereditary angioedema. Short-term studies of such patients treated at our institution with attenuated androgens demonstrated no adverse effects. However, the side-effect frequencies in patients receiving long-term treatment are relatively less well characterized. OBJECTIVE: To assess the frequencies of various side effects of the attenuated androgen stanozolol in a population of patients with hereditary angioedema treated for 20 to 40 years. METHODS: Data on side effects in patients who continued stanozolol therapy since 1987 were obtained by means of questionnaire. Patients were evaluated by physical examination; biochemical assays of hepatic function, serum lipids, and prostate specific antigen; and liver ultrasound. RESULTS: The minimal initial effective dosage of stanozolol was 0.5 to 2.0 mg daily, although most patients achieved symptomatic control and decreased the dose and frequency as the frequency of attacks decreased. Treatment-related symptoms developed in 10 of 21 patients. No interruption in stanozolol therapy was required because symptoms subsided with a reduction in the stanozolol dosage. Adverse side effects included hirsutism, weight gain, menstrual irregularities or postmenopausal bleeding, acne, and mood changes. Liver enzyme assays revealed no persistent abnormalities. Liver ultrasounds in 8 patients revealed 3 abnormalities deemed unrelated to therapy. Five patients had a reduced high-density lipoprotein, and 2 patients had elevated triglycerides. CONCLUSION: Stanozolol is a safe and effective drug for the long-term management of hereditary angioedema. CLINICAL IMPLICATIONS: Stanozolol may be used in the long-term treatment of patients with hereditary angioedema provided such patients are closely supervised with routine clinical, biochemical, and radiologic assessments.

Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses.

OBJECTIVES: Hypersensitivity reactions (HR) to chemotherapy often prompt permanent discontinuation and deprive the patient of the most active regimen. We investigated the safety and effectiveness of a rapid desensitization protocol used in inpatient and outpatient settings for patients with HR to various chemotherapy and related agents. METHODS: A 3-solution, 12-step protocol delivered doubling drug doses by step, infusing the target dose over 5.8 h for inpatient and 3.8 h for outpatient administration. RESULTS: 57 consecutive patients who had moderate to severe HR to chemotherapy were evaluated for desensitization. All 57 patients successfully completed 255 courses of desensitization (127 to carboplatin, 114 to paclitaxel, and 14 to four other agents) where 16 patients received 51 courses in the outpatient setting (34 to carboplatin and 17 to paclitaxel). 225 courses (88.2%) were completed without any HR. 18 patients had breakthrough symptoms (BS) over 30 courses (11.8%) that were less severe than their initial HR. After management of breakthrough symptoms, these patients finished all 30 courses and tolerated subsequent desensitizations on a modified protocol. 21 of 26 patients (81%) with HR to carboplatin had positive skin tests to carboplatin. Cancer response to chemotherapy administered by desensitization was within the expected range after 1-3 years of follow-up. CONCLUSION: The rapid desensitization protocol was safe and effective in both the inpatient and outpatient settings and allowed appropriate patients with moderate to severe HR to continue chemotherapy. This study warrants the incorporation of the protocol into standard clinical practice.

Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments.

OBJECTIVE: Administration of paclitaxel is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication. The purpose of this study was to evaluate the effectiveness of a standardized desensitization protocol in patients with HSRs to taxanes, based on our experience with carboplatin desensitization. METHODS: We analyzed seventeen consecutive patients with documented HSRs to taxanes who required continued treatment with a taxane agent. The patients were treated with either paclitaxel or docetaxel using the 6- to 7-h standard desensitization protocol. RESULTS: Seventeen patients who previously had severe taxane HSRs successfully completed 77 planned cycles of desensitization to paclitaxel or docetaxel, 72 of which were without reactions. Four patients developed HSRs during the desensitization protocol that were much less severe than their original HSRs and tolerated the re-administration of infusions without further reactions. Of these four patients, the first had palmar erythema 8 h after her 1st desensitization. The second patient had mild abdominal pain during her 1st cycle, and the third patient developed mild chest burning during her 2nd and 4th cycles. These three patients also completed subsequent desensitization cycles without reactions. The fourth patient developed a delayed urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st desensitization. She elected to be treated with an alternative chemotherapy and did not receive additional courses of desensitization. CONCLUSION: The rapid standard desensitization protocol provides a safe and effective strategy for the re-administration of paclitaxel or docetaxel even after severe HSRs.

Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions.

OBJECTIVES: The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR. METHODS: We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6-h, 12-step desensitization protocol with a 30-min premedication regimen. Skin tests were performed on five patients. RESULTS: Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re-administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. CONCLUSION: The 6-h, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen-specific mast cell desensitization.

Perioperative anaphylaxis to cefazolin.

The incidence of generalized reactions during anesthesia has been reported to range from 1 in 5000 to 1 in 25,000 cases with a mortality rate of up to 6%. The most common causes are neuromuscular blocking agents, latex, and antibiotics. Identification of the offending agent may be difficult because multiple medications are administered over a short period. Furthermore, up to 40% of all generalized reactions during anesthesia are non-immunoglobulin E mediated and therefore can not be evaluated by skin testing. We report a case of perioperative anaphylaxis to cefazolin. Sensitization to cefazolin was determined through skin testing, and the patient underwent successful surgery subsequently with the avoidance of cefazolin.

Peanut allergy.

Peanut allergies have become a major health concern in the United States. Peanuts are one of the most common causes of food allergies and along with tree nuts they account for most of the cases of fatal and near-fatal anaphylactic reactions to food. Not only is there a rise in the prevalence of peanut allergies in Westernized countries but also most patients with peanut allergies have lifelong clinical sensitivities to peanuts. Patient management involves strict avoidance, recognition of the early symptoms of anaphylaxis, and usage of an emergency treatment plan, including the self-administration of epinephrine in case of an accidental ingestion. Future treatment strategies may include recombinant peanut protein immunotherapy and anti-Immunoglobulin E therapy to modulate clinical reactivity to peanuts. This article reviews the current understanding of the clinical characteristics, pathogenesis, diagnosis, and management of the peanut allergy.

Primary acquired cold urticaria.

Primary acquired cold urticaria (ACU) is the most common type of cold urticaria characterized by rapid onset of pruritic hives, swelling, and possible severe systemic reactions including hypotension and shock after cold exposure. Primary ACU is diagnosed by history of such symptoms, a positive immediate cold-contact stimulation test, and negative laboratory evaluation for underlying systemic disorders. Clinicians should be aware that patients with ACU may be susceptible to life-threatening systemic reactions especially during aquatic activities and that proper patient education is extremely important. This article reviews the clinical presentation, pathogenesis, diagnosis, and management of primary ACU.