Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

BACKGROUND: The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. OBJECTIVE: To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. METHODS: Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. RESULTS: By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. CONCLUSIONS AND CLINICAL RELEVANCE: In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions.

Angiotensin-converting enzyme inhibitors do not impair the safety of Hymenoptera venom immunotherapy build-up phase.

BACKGROUND: There is an ongoing debate on whether angiotensin-converting enzyme inhibitors (ACEI) should be substituted prior to initiation of venom immunotherapy (VIT) for safety reasons. OBJECTIVE: We aimed to assess the influence of ACEI medication on the incidence of systemic reactions (SR) during the build-up phase of VIT in a large and homogeneous cohort of patients. METHODS: The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed in relation to cardiovascular medication, age, sex, venom, reactivity in diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities, latency before the initiation of VIT, and treatment protocols. ACEI were routinely maintained throughout VIT, beta-blockers replaced if appropriate. RESULTS: During VIT-initiation, 190 (24.5%) patients were on some kind of cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT-related SR rates were 11.7% (any documented reactions including subjective symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of anaphylaxis). Medication with ACEI (P = 0.097) or beta-blockers (P = 1.0) was not significantly related to the incidence of SR. A reduced rate of SR in patients taking cardiovascular drugs was not statistically significant in the final multivariate regression model. A prolonged latency before the initiation of VIT (P = 0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush protocols (P = 0.008, odds ratio = 3.522) increased the frequency of SR. CONCLUSIONS AND CLINICAL RELEVANCE: Study data do not provide evidence of an ACEI-mediated increase of VIT-related SR, supporting the continued use of these valuable and hard-to-replace substances throughout VIT.

[Anetodermic pilomatricoma. Uncommon variant of a common childhood adnexal tumor]. / Anetodermisches Pilomatrikom. Seltene Variante eines häufigen Adnextumors im Kindesalter.

The anetodermic ("bullous") subtype is a rare variant of pilomatricoma which we diagnosed in 2 girls who were 9 and 10 years old. The tumors presented as 3 × 2 and 1.5 × 1.5 cm red dome-shaped nodules with a slightly wrinkled surface on the upper back and on the pretibial region, respectively. Both were superficially soft, but then firm as one palpated deeper. Histology showed an edematous, well-vascularized dermis resembling granulation tissue overlying a deep otherwise typical pilomatricoma. Clinical and histological characteristics of the anetodermic subtype are discussed on the basis of previously published cases.

A case of lymphomatoid papulosis limited to Becker's melanosis.

Regional lymphomatoid papulosis (LyP) accounts for 2-27% of all LyP cases. Several localized dermatoses have been reported in association with Becker's melanosis (BM), e.g. acneiform lesions or lichen planus. Here, we report on regional LyP confined to the area of BM. A 56-year-old man presented with a 1-year history of a steadily increasing number of multiple pruritic red papules developing on the area of BM, which had occurred on his left shoulder during puberty. Histopathological analysis was consistent with regional LyP. Potent topical steroids followed by oral doxycycline did not achieve improvement, while long-term oral bexarotene treatment ameliorated the skin condition. Recently, the proposed entity of 'persistent agmination of LyP' (PALP) has extended the clinicopathological observations of regional LyP. Since PALP remains controversial, a unifying concept of localized LyP and PALP will be discussed.

[Persistent swelling after flushing of an abscess with Octenisept®]. / Persistierende Schwellung nach Spülung eines Abszesses mit Octenisept®.

We report the case of a long-lasting cutaneous side effect after inappropriate use of Octenisept® solution (containing octenidine and phenoxyethanol). Following lavage of an abscess in the inguinal region, a painful erythematous induration mimicking cellulitis persisted for several months. Manual lymphatic drainage considerably improved the symptoms. Octenisept® shows considerable tissue toxicity in vivo including - but not restricted to - blood vessel damage. Deterioration of endothelial cells followed by oedema and continued tissue damage can be seen histologically. Despite the fact that there is a circular letter issued by the manufacturer as well as a boxed warning on the bottles, the awareness to avoid this misuse of Octenisept® is still lacking.

Further evidence for the efficacy of a metacognitive group training in schizophrenia.

Metacognitive training (MCT) for patients with schizophrenia is a novel psychological group treatment targeting cognitive biases putatively involved in the pathogenesis of schizophrenia (e.g. jumping to conclusions, overconfidence in errors). Its eight modules are available cost-free online in many languages. In the present study, 36 subacute or remitted patients were randomly allocated to either the MCT or a wait-list group who received treatment-as-usual (TAU). Baseline and post assessments were 8 weeks apart and were performed blind to group status. MCT showed significantly greater improvement on the following parameters relative to the TAU group: delusion distress (PSYRATS), memory and social quality of life. In the MCT group, the rate of jumping to conclusions bias was reduced after training. No differences occurred on the PANSS. The present study confirms prior reports that MCT exerts beneficial effects on some cognitive and symptomatic parameters.

Who is really in control of skin immunity under physiological circumstances - lymphocytes, dendritic cells or keratinocytes?

Our views of the skin immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and skin biology, but also have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as 'lead actors' on the skin immunity stage, the lowly keratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate skin immunity system, which may control even acquired skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as 'stage managers' pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance - complete with the impresario's overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talents and even the critic's digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play - at least for the time being...

Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed.

Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes.

The transcription factor NF-ATc that controls gene expression in T lymphocytes and embryonic cardiac cells is expressed in three prominent isoforms. This is due to alternative splice/polyadenylation events that lead to the predominant synthesis of two long isoforms in naive T cells and a shorter NF-ATc isoform in effector T cells. Whereas the previously described isoform NF-ATc/A contains a relatively short C terminus, the longer isoforms, B and C, span extra C-terminal peptides of 128 and 246 aa, respectively. We show here that in addition to the strong N-terminal trans-activation domain, TAD-A, which is common to all three NF-ATc isoforms, NF-ATc/C contains a second trans-activation domain, TAD-B, in its C-terminal peptide. Various stimuli of T cells that induce the activity of TAD-A also enhance the activity of TAD-B, but, unlike TAD-A, TAD-B remains unphosphorylated by protein from 12-O-tetradecanoyl 12-phorbol 13-acetate-stimulated T cells. The shorter C-terminal peptide of isoform NF-ATc/B exerts a suppressive transcriptional effect. These properties of NF-ATc/B and -C might be of importance for gene regulation in naive T lymphocytes in which NF-ATc/B and -C are predominantly synthesized.

Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells.

The transcription factor NF-ATc is synthesized in three prominent isoforms. These differ in the length of their C terminal peptides and mode of synthesis. Due to a switch from the use of a 3' polyA site to a more proximal polyA site, NF-ATc expression switches from the synthesis of the two longer isoforms in naive T cells to that of short isoform A in T effector cells. The relative low binding affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems to contribute to its neglect in naive T cells. These alternative polyadenylation events ensure the rapid accumulation of high concentrations of NF-ATc necessary to exceed critical threshold levels of NF-ATc for gene induction in effector T cells.