Aspirin treatment of patients with aspirin intolerance, asthma, and nasal polyps.

Patients with the triad of aspirin (ASA) intolerance, asthma, and nasal polyps present a clinical challenge for the allergist because their polyps generally are refractory to traditional treatments and their asthmatic symptoms may become more difficult to control with time. These patients can be desensitized and treated with ASA with subsequent improvement in their nasal and respiratory symptoms. This article describes one such individual and briefly reviews the literature regarding this triad. The diagnosis of ASA intolerance, mechanistic studies, a desensitization protocol, and new therapies are reviewed.

Exercise-induced anaphylaxis (EIA).

EIA is a unique physical allergy with increasing incidence as the exercising population increases. Clinical features are indistinguishable from IgE-mediated anaphylaxis in which the offending allergens are known (food or insect stings). Recognition of the association with exercise is crucial. A wide variety of exercises can induce the symptoms, including brisk walking. Symptoms may not be always reproduced by the same amount and type of exercise in a given patient suggesting that associated factors are also needed. Food is an associated factor recognized with increasing frequency, and in the last 5 yr, wheat has been the most frequently associated. Avoidance of the known associated factors, such as food or nonsteroidals, induces a long-lasting remission of EIA. Treatment does not differ from that of anaphylaxis of any other cause. General recommendations for patients with EIA include avoidance of exercise 4-6 h after eating, avoidance of aspirin and nonsteroidals before exercise, and avoidance of all associated conditions known to trigger attacks in each particular patient. Discontinuation of exercise at the earliest warning symptom is critical.

Stevens-Johnson-type reaction with vancomycin treatment.

OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin. CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation. Its pathogenesis is poorly understood. Mortality rates have ranged from 30 to 100 percent. We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 71-year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site. Classic "target" lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient. DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome. Serious cutaneous reactions to vancomycin, however, have been uncommon. Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms. CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome.

Physical allergies.

Allergic responses that occur as a result of exposure to physical stimuli are discussed. Most of these conditions are mediated by vasoactive substances, resulting in urticaria and/or angioedema. Susceptible individuals who engage in athletic activities may place themselves at particular risk for these problems. The physical allergies include cholinergic urticaria, exercise-induced anaphylaxis, cold urticaria, dermatographism, solar urticaria, and aquagenic urticaria. Management of these conditions includes patient education, selective avoidance, antihistamines, and, in some cases, induction of tolerance.

Mast-cell phenotype in indolent forms of mastocytosis. Ultrastructural features, fluorescence detection of avidin binding, and immunofluorescent determination of chymase, tryptase, and carboxypeptidase.

The factor(s) that causes excessive mast cell (MC) proliferation in indolent forms of mastocytosis is not known, nor is it known whether that proliferation is a regulated clonal expansion or merely a non-neoplastic hyperplasia. Human MCs display phenotypes that depend on the microenvironment. Thus, if the phenotype of MCs in mastocytosis lesions is determined to be abnormal for that tissue site (and therefore the MCs are refractory to microenvironmental signals) then a clonal process would be suggested. The authors determined the phenotypes of MCs from the lesional skin of 17 patients with indolent mastocytosis and the bone marrows of 9 patients. They compared them with the phenotypes of MCs from the lesional skin of 8 patients with various dermatitides, the skin of 2 patients with idiopathic anaphylaxis, and the breast skin of 15 control patients. MCs from all the skin specimens showed the characteristic skin MC phenotype, with predominantly scroll-poor granules by ultrastructure and containing tryptase and chymase by immunofluorescence detection (the MCTC immunophenotype). The skin MCs of each patient bound avidin and contained carboxypeptidase by immunofluorescence detection. MCs from the bone marrow of patients with indolent mastocytosis, the source of progenitors, also showed the scroll-poor and MCTC phenotypes. These findings do not support an unregulated clonal expansion in indolent forms of mastocytosis. They are consistent with a non-neoplastic hyperplasia or possibly a clonal process in which MCs remain responsive to microenvironmental regulation.

Systemic mastocytosis: retrospective review of a decade's clinical experience at the Brigham and Women's Hospital.

The clinical experience with a group of 21 patients with systemic mastocytosis followed at our institution is summarized. Cutaneous and gastrointestinal symptoms and findings were the most prominent chronic manifestations; episodic vascular collapse was the most dramatic acute event. All patients had indolent mastocytosis. There was no mortality.

Systemic mastocytosis: retrospective review of a decade's clinical experience at the Brigham and Women's Hospital.

The clinical experience with a group of 21 patients with systemic mastocytosis followed at our institution is summarized. Cutaneous and gastrointestinal symptoms and findings were the most prominent chronic manifestations; episodic vascular collapse was the most dramatic acute event. All patients had indolent mastocytosis. There was no mortality.

Characterization of cellular dermal infiltrates in human cutaneous mastocytosis.

Biopsies of lesional and nonlesional skin from 14 patients with localized cutaneous or associated systemic mastocytosis were examined by ultrastructural and immunohistochemical techniques. Mast cells within lesions of the dermis were highly variable between patients with regard to cell number and extent of degranulation, although lesional sites consistently contained more mast cells than did nonlesional sites. Two mast cell patterns were identified based upon granule morphology. In biopsies from 8 patients, the majority of granules contained electron-dense amorphous zones; crystalline lattices; and indistinct, incomplete solid scrolls forming parallel lamellae. In biopsies from 6 patients, in addition to these granules, there were also granules composed of electron-dense amorphous zones, reticulated matrices, and/or distinct scrolls with lucent cores interrupted by dense spheres. The granule morphology for the first group (N = 8) was identical with that seen in the preponderant type of skin mast cell of 6 normal control subjects, whereas the granule morphology of the second group (N = 6) displayed an abnormal ultrastructural phenotype for skin that included granule types normally found not only in skin but also in intestinal lamina propria and lung. For individual patients, the patterns of granule ultrastructure were consistent between clinically nonlesional and lesional skin. A minority of cells in both patient groups appeared primitive ultrastructurally, exhibiting rudimentary, Golgi-associated progranules; monocyte-like morphologic characteristics; and mitotic activity. Moreover, when mast cells in lesional skin were screened for a limited panel of surface antigens, they displayed common patterns of reactivity (M718+, HLA-DR/DQ+, CD4+), and in a selected case, immunoelectron microscopy confirmed the presence of these antigens on mast cell plasma membranes. Dermal mast cells from normal donors (N = 6) lack these epitopes. These observations suggest that infiltrates in cutaneous mastocytosis may exhibit phenotypic characteristics not only of cutaneous mast cells, but in some patients also of mucosal mast cells. In either circumstance, the mast cells may display antigenic determinants common to monocyte/macrophages. Concordance of granule phenotype between lesional and clinically uninvolved skin of individual patients furthers the notion that even localized mastocytosis reflects covertly defective systemic mast cell homeostasis.

Cromolyn sodium in the management of systemic mastocytosis.

A multicenter, double-blind, placebo-controlled trial of the efficacy of oral cromolyn sodium (200 mg orally four times per day) was conducted in 11 patients with systemic mastocytosis who had been maintained with the drug on an individualized compassionate-need basis. Efficacy was measured by physician assessment of overall disease severity based on history and physical examination at specified intervals and by the average daily patient symptom diary scores for each of three mastocytosis-related symptoms that had previously appeared to be alleviated by the use of this drug. Efficacy variables were compared for a 4-week baseline period, during which patients received open-labeled cromolyn sodium, and at 4-week intervals during a 16-week period of random assignment to cromolyn sodium or placebo. Overall disease severity and symptoms recorded in patient diaries were graded on a scale of 0 (absent) to 5 (incapacitating). The average physician assessment of disease severity and symptom scores of the patients in the placebo-treated group increased significantly during the randomization phase relative to patients in the cromolyn sodium-treated group, reflecting an exacerbation of symptoms with drug withdrawal (p less than 0.05 and less than 0.028, respectively). When the symptom scores were analyzed separately for gastrointestinal manifestations of disease (diarrhea, abdominal pain, nausea, and vomiting), cromolyn sodium treatment was significantly beneficial relative to placebo (p less than 0.02), whereas the benefit for nongastrointestinal manifestations did not reach statistical significance.

Current concepts of urticaria and angioedema.

An operational classification based on immunoreactants provides insight to possible pathogenetic mechanisms participating in the genesis of urticaria and angioedema. Such an approach addresses the causes of urticaria and angioedema. Therapy can then be developed depending on the established mechanism-etiology. Unfortunately, in less than a third of the instances can a distinct etiology be established, but symptomatic therapy provides relief in a significant portion of such afflicted individuals.

Atypical angiomatosis in polyarteritis nodosa.

Biopsies from an area of livedo reticularis and adjacent to a leg ulcer in a woman with polyarteritis nodosa showed florid angioendothelial proliferation simulating angiosarcoma. This angioproliferative reaction has not been described previously in polyarteritis nodosa. Its microscopic differentiation from angiosarcoma is important.

Acute hemolysis and renal failure with rifampicin-dependent antibodies after discontinuous administration.

Acute hemolysis as a reaction to rifampicin is extremely rare; case reports number less than 15. We recently evaluated a 65-year-old Cambodian refugee who self-regulated the use of rifampicin and isoniazid for pulmonary tuberculosis. Fifteen minutes after a single discontinuous oral dose, he developed flank pain, chills, rigors, vomiting, diarrhea, fever, and brown turbid urine. Laboratory tests at presentation showed acute intravascular hemolysis. Nonoliguric renal failure ensured, and he was transferred to our institution 2 days later. The patient was group A, Rh (D) positive, P1 negative with a cold autoantibody and cold anti-P1 alloantibody. The direct antiglobulin test was negative at the time of transfer. To evaluate the hemolysis, studies were done to test for rifampicin- or isoniazid-dependent antibodies. Rifampicin-dependent antibodies were detected in the antiglobulin phase with broad spectrum anti-human globulin, monospecific anti-gamma chain, and anti-complement antisera. Agglutination titers did not change after dithiothreitol reduction of the patient's serum. We conclude that this patient developed rifampicin-dependent IgG antibodies with complement-fixing capability. The presence of rifampicin-dependent antibodies should be suspected in a patient with hemolysis and/or renal failure taking rifampicin.

LH-RH testing in men with Down's syndrome.

Males with Down's syndrome frequently present incomplete sexual development and are presumed to be sterile. The intent of this study is to clarify the aetiology of diminished sexual function in men with trisomy 21. Single dose LH-RH stimulation tests were performed in 6 men with Down's syndrome. Compared to a control group of 6 mentally retarded, institutionalized males, the subjects with Down's syndrome had markedly elevated basal FSH and slightly elevated basal LH concentrations. The FSH response to LH-RH stimulation was notably increased in the Down's syndrome group, while the LH response showed a lesser increase. Testosterone concentrations were found to be comparable in the two groups. The results are consistent with the clinical assumption that males with Down's syndrome have decreased spermatogenesis and infertility and that their Leydig cell function is less affected.