Overview of Penicillin Allergy

Allergy to penicillin is the most commonly reported antibiotic allergy. However, most patients who report a positive history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing. Often, this history is vague or based on a parent's recollection of an event that occurred in the distant past. Avoidance of penicillin based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. Patients with a negative skin test to both major and minor determinants may generally be given penicillin, with a statistical risk of developing an allergic reaction similar to that observed in the general population. A more cautious approach in these cases where the degree of suspicion is low, an allergic etiology is unproven, or there is a negative skin test, is to do a graded challenge. If the skin test is positive, an alternate antibiotic should be used. If, however, an alternate antibiotic is not available, then desensitization may be performed, but there are limitations to desensitization as well, and tolerance is not permanent. Avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cephalosporins have demonstrate less cross-reactivity to penicillin than earlier generation ones. Desensitization protocols for cephalosporins are available but not standardized. The mechanisms of antibiotic sensitization are not clearly understood.     

Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies

Stiff Person Syndrome (SPS) is a rare autoimmune neurological disease attributable to autoantibodies to glutamic acid decarboxylase (anti-GAD) more usually associated with the islet beta cell destruction of autoimmune type 1 diabetes (T1D). SPS is characterized by interference in neurons with the synthesis/activity of the inhibitory neurotransmitter gamma amino butyric acid (GABA) resulting in the prototypic progressive spasmodic muscular rigidity of SPS, or diverse neurological syndromes, cerebellar ataxia, intractable epilepsy, myoclonus and several others. Remarkably, a single autoantibody, anti-GAD, can be common to widely different disease expressions, i.e. T1D and SPS. One explanation for these data is the differences in epitope engagement between the anti-GAD reactivity in SPS and T1D: in both diseases, anti-GAD antibody reactivity is predominantly to a conformational epitope region in the PLP- and C-terminal domains of the 65 kDa isoform but, additionally in SPS, there is reactivity to conformational epitope(s) on GAD67, and short linear epitopes in the C-terminal region and at the N-terminus of GAD65. Another explanation for disease expressions in SPS includes ready access of anti-GAD to antigen sites due to immune responsiveness within the CNS itself according to intrathecal anti-GAD-specific B cells and autoantibody. Closer study of the mysterious stiff-person syndrome should enhance the understanding of this disease itself, and autoimmunity in general.     

Nachweis und Bedeutung antinucleärer Antikörper in der Diagnostik der Erkrankungen des rheumatischen Formenkreises

Zusammenfassung Antinucleäre Antikörper und Anti-DNS-Antikörper wurden in den Seren von 60 Patienten, die an einem Lupus erythematodes disseminatus und 40 Patienten, die an einer rheumatoiden Arthritis erkrankt waren, bestimmt. Antinucleäre Faktoren ließen sich mit den verschiedenen Methoden in unterschiedlicher Häufigkeit und Titerhöhe nachweisen. Insgesamt wurden 9 verschiedene Untersuchungsmethoden für z.T. unterschiedliche Antikörperspezifitäten angewandt. Für die Anwendung in der Klinik erscheint eine Kombination verschiedener Techniken für die Diagnostik und Verlaufsbeobachtungen am ehesten geeignet, um neben dem pauschalen Nachweis der antinucleären Antikörper insgesamt einige spezifische Antikörperbefunde zu erfassen. Für Verlaufsbeobachtungen beim Lupus erythematodes disseminatus ist die radioimmunologische Bestimmung mit Hilfe eines Farr-Assays oder einer Doppelantikörpertechnik und wenn möglich simultaner Bestimmung der Antikörper gegen Einzelstrangund Doppelstrang-DNS am sinnvollsten.     

Changing patterns of childhood aphasia

Acquired aphasia in children has been generally characterized as nonfluent, transient, and frequently due to right hemisphere lesions. We studied 65 children with unilateral hemispheric brain lesions occurring after speech acquisition any time from the second through the fourteenth year. Of 34 patients with a left hemisphere lesion, 25 had an initial aphasic speech disturbance, while of 31 patients with a right hemisphere lesion, only 4 (including 2 lefthanders) showed any initial aphasia. All those who became aphasic before the age of 8 years eventually regained speech, but recovery time required ranged from less than a month to more than two years. One 5-year-old boy who recovered had initial jargon aphasia. Our review of the literature indicated that the conflict between our results and the traditional claim of frequent aphasia with right hemisphere lesions was only apparent; the great majority of crossed aphasias are concentrated in reports written before antibiotics were used, and many cases were associated with systemic bacterial infections.     

Intrathecal production of neopterin in meningitis in childhood

A major activator of antigen presenting cells (APC) is gamma interferon a product of activated T-lymphocytes. CNS is not well studied and represents a unique system with respect to the immune reactions. Neopterin is an indirect marker of gamma interferon deliberation and may give some new information on the role of APC in CNS. Neopterin in serum and cerebrospinal fluid (CSF) was determined by specific RIA in children who were lumbar punctured to exclude meningitis. Neopterin was found in various concentrations in serum and CSF of all patients (n = 47). Bacterial meningitis (group 3) was diagnosed in 12 and aseptic meningitis in 18 children (group 2). CSF was drawn in 17 children with febrile convulsions (group 1). Elevated serum neopterin in childhood was only reported in children with an atypical PKU, while data on CSF neopterin were published only in a few cases of adults with CNS involvement. The results show that the APC is stimulated rapidly in childhood similar as in adults following severe viral or bacterial infections. Furthermore neopterin in CSF is not only explained by alteration of the blood-brain barrier but also it may reflect local intrathecal response with activation of accessory cells (APC) in the CNS itself. Between the stimulation of the cellular immune system indicated by increased levels of neopterin and the severity of the disease seems to be a positive correlation.     

Identification and cloning of a complementary DNA encoding a vicilin-like proprotein, jug r 2, from english walnut kernel (Juglans regia), a major food allergen

BACKGROUND: Walnuts and other tree nuts are important food-allergen sources that have the potential to be associated with life-threatening, IgE-mediated systemic reactions in some individuals. OBJECTIVE: The purpose of this study was to characterize a complementary (c)DNA clone encoding one of the walnut food allergens. METHODS: A cDNA expression library prepared from walnut somatic embryo was screened for IgE reactivity with patient serum. A reactive clone of 2060 bp, which encoded a protein of 593 amino acids in length, was subcloned by excision into the pGEX expression vector. IgE-binding inhibition experiments were performed. RESULTS: A recombinant fusion protein was induced and shown to bind serum IgE from 9 of 15 patients tested, thus identifying a major allergen. This clone, named Jug r 2, exhibited significant homology with genes encoding the vicilin group of seed proteins. An IgE-binding inhibition experiment suggested that the encoded protein undergoes posttranslational modification into at least one major polypeptide (47 kd) and possibly several others, which is similar to the vicilin-like proteins characterized in cocoa bean (Theobroma cacao) and cottonseed (Gossypium hirsutum). N-terminal sequencing of the 47-kd band, Jug r 2, identified it as a mature protein obtained from the precursor. A second IgE-binding inhibition experiment showed that there is minimal or no cross-reactivity between Jug r 2 and pea vicilin, peanut proteins, or cacao proteins. CONCLUSION: Jug r 2 is the third vicilin food allergen identified in addition to vicilins from soy and peanut. The availability of recombinant food allergens should help advance studies on the immunopathogenesis and possible treatment of IgE-mediated food hypersensitivity.     

Food allergy diagnostics: scientific and unproven procedures

PURPOSE OF REVIEW: The accurate diagnosis of food allergy is crucial not only for the right treatment but also for the avoidance of unnecessary diets. The diagnostic work-up of suspected food allergy includes the measurement of food-specific IgE antibodies using serologic assays, the skin prick test, elimination diets and oral provocation tests. In addition, some approaches are either under further rigorous investigation (the atopy patch test) or are already in widespread use, particularly by practitioners of alternative or complementary medicine, but are considered unproven. These diagnostic methods include specific IgG to foods, provocation/neutralization testing, kinesiology, cytotoxic tests and electrodermal testing. This review covers some of the most common scientifically validated and unproven approaches used in the diagnosis of food allergy. RECENT FINDINGS: For specific serum IgE and the SPT, decision points have been established for some foods, allowing prediction of clinical relevance. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. In regard to other approaches, most scientific studies do refute the usefulness of these approaches. SUMMARY: In most patients, controlled oral food challenges remain the gold standard in the diagnostic work-up of suspected food allergy. The skin prick test and measurement of specific IgE antibodies to food extracts, individual allergens or allergenic peptides are helpful in the diagnostic approach. Food-specific IgG continues to be an unproven or experimental test. The other alternative and complementary techniques have no proven benefit and may endanger patients via misdiagnosis.     

Thyrotoxic crisis in Graves' disease: Indication for immediate surgery

Summary Thyrotoxic crisis (thyroid storm) is a rare complication of hyperthyroidism. It can be observed not only in thyroid autonomy with latent hyperfunction after exposure to iodine, but also in Graves' disease with overt hyperfunction. Adequate management of thyrotoxic crisis is still controversial. We report about four patients (four women, mean age 75 years) with Graves' disease who developed thyrotoxic crisis during therapy with antithyroid drugs so that surgical intervention became necessary. The patients had been admitted to the hospital for nonspecific symptoms such as headache, cachexy, and psychosis. Thyroid hormone levels had reached twice the normal range prior to surgery. All patients showed severe neurological deficits leading to coma. In three cases euthyroidism was achieved within two days after surgery. The neurological symptoms disappeared after an average of four days. The postoperative course did not show severe complications and all patients recovered completely.Especially in the elderly a monosymptomatic or nonspecific course of thyroid storm with neurological symptoms may represent a severe and life-threatening situation. In these cases surgery can become necessary even if euthyroidism has not been achieved preoperatively.Abbreviations dl deciliter - FT3 free triiodthyronine - FT4 free thyroxine - Hg mercury - l liter - MAK microsomal antibodies - mg milligram - ml milliliter - mU milliunit - ng nanogram - T3 triiodthyronine - T4 thyroxine - TAK thyroglobulin antibodies - TBG thyroxine-binding globulin - TRAK TSH-receptor antibodies - TRH thyrotropin-releasing hormone - TSH thyroid-stimulating hormone - TT3 total triiodthyronine - TT4 total thyroxine - g microgram