Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal,flare and itch in human skin

Objective: A previous study showed the inhibitory effects of loratadine on histamine-induced wheal, flare and itch in human skin to be very variable between individuals. It was hypothesised that this variability may have been due to differences in the rates of metabolism of loratadine to its active form, desloratadine. This double blind, crossover study examined the effects of desloratadine in 12 healthy volunteers. Levocetirizine was used as a comparator. Methods: Desloratadine (5 mg), levocetirizine (5 mg) or placebo was taken orally 4 h before an intradermal injection of histamine (20 l, 100 M) or vehicle control into the forearm skin. Flare areas were assessed by scanning laser Doppler imaging before and at 30 s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s for 5 min using a visual analogue scale. Results: Following placebo administration, the mean (± SEM) wheal area at 10 min was 79.3 ± 6.9 mm², mean flare area for the first 5 min following challenge 26.6 ± 2.7 cm², and itch score for the same period 48.5 ± 7.6%. The effects of desloratadine were variable between individuals, mean reductions in the wheal and flare areas being 17% (P = 0.033) and 12% (P = 0.036). Desloratadine did not reduce itch significantly. Levocetirizine was more consistent in its effects, mean reductions in wheal, flare and itch being 51%, 67% 78% respectively (all P < 0.001). Conclusions: A single dose of 5 mg levocetirizine produced more consistent and greater inhibitory effects on histamine-induced wheal, flare and itch than did 5 mg desloratadine. The difference is suggested to reflect the basic pharmacokinetics of the two drugs.Received 21 May 2003; returned for revision 29 May 2003; accepted by M. Parnham 5 June 2003     

A comparison of levocetirizine and desloratadine in the histamine-induced wheal and flare response in human skin in vivo

Background The histamine-induced wheal and flare response was used to compare quantitatively the antihistaminic potency of levocetirizine and desloratadine. Methods In this double-blind, placebo-controlled crossover study, 24 healthy male non-atopic volunteers received weekly single doses of 1.25, 2.5 or 5 mg levocetirizine, 2.5, 5 or 10 mg desloratadine, or placebo. Four hours after dosing, histamine (100 mg/ml) skin prick tests were performed on the volar surface of both forearms. The diameters of the wheals and flares were measured 10 minutes later. Sedation was evaluated using a visual analogue scale and a motricity test. The effects of individual drug doses were compared using Student’s t-test for paired data and the overall effects of the two drugs by ANOVA. Results All doses of levocetirizine significantly (P < 0.0001) inhibited both wheals and flares in a dose-related manner. Only the 10 mg dose of desloratadine achieved significant inhibition of response. ANOVA showed levocetirizine to be significantly (P < 0.0001) more active than desloratadine. Neither drug caused significant sedation or loss of motricity. Conclusion Levocetirizine is significantly more effective than desloratadine in inhibiting wheal and flare responses to histamine in human skin in vivo, with 1.25 mg levocetirizine being more effective than 10 mg desloratadine. Received 3 July 2005; returned for revision 9 August 2005; returned for final revision 6 February 2006; accepted by M. Parnham 8 February 2006     

Montelukast with desloratadine or levocetirizine for the treatment of persistent allergic rhinitis.

BACKGROUND: Montelukast sodium is approved as a treatment for intermittent and persistent allergic rhinitis (AR), but it has not been evaluated as combined therapy with antihistamines for persistent AR. OBJECTIVE: To investigate the effects of 6 weeks of treatment of persistent AR with desloratadine, levocetirizine, or montelukast alone or in combination. METHODS: A randomized, double-blind, placebo-controlled crossover study was performed. Patients were assigned to 2 arms: 20 received montelukast, 10 mg/d, desloratadine, 5 mg/d, or both or placebo and 20 received montelukast, levocetirizine, or both, 5 mg/d, or placebo. The treatment periods were separated by 2-week washout periods. Symptom scoring, skin prick tests, spirometry, rhinometry, and nasal lavage were performed the day before and the last days of the treatment periods. Eosinophil cationic protein levels were evaluated by means of nasal lavage. RESULTS: The mean +/- SD total baseline nasal symptom score was 7.7 +/- 0.49 before treatment, 3.74 +/- 0.54 after desloratadine use, 3.6 +/- 0.48 after montelukast use, and 3.04 +/- 0.4 after montelukast-desloratadine use. The mean +/- SD baseline nasal symptom score was 7.95 +/- 0.68 before treatment, 3.02 +/- 0.64 after levocetirizine use, 3.44 +/- 0.55 after montelukast use, and 2.14 +/- 0.39 after montelukast-levocetirizine use. The greatest improvement in nasal symptoms occurred after combination treatment. Decreases in the level of eosinophil cationic protein were greater after the combined use of montelukast and antihistamine than after each agent given alone. CONCLUSIONS: For persistent AR, the combination of montelukast and either desloratadine or levocetirizine is more effective than monotherapy with these agents.     

Reliability of allergy skin testing

Background

Percutaneous allergen skin testing remains an established benchmark for diagnosing atopic disease. The reliability of skin testing depends greatly on the performance of allergen extracts used, methods used, and the presence of antihistamine medications.

Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours.

BACKGROUND: Cetirizine and desloratadine are antihistamines active in the treatment of symptoms associated with seasonal allergic rhinitis and chronic urticaria. OBJECTIVE: To compare the antihistamine activity of desloratadine, the active metabolite of loratadine, with that of cetirizine in the skin wheal-and-flare responses during 24 hours. METHODS: This was a double-blind, randomized, placebo-controlled, single oral dose, crossover study. Skin reaction to histamine (100 mg/mL), administered by prick tests, was measured by the wheal and flare surface areas for 24 hours (before treatment and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours). Eighteen healthy volunteers (mean age, 33.9 years; 13 women) participated in this study. The areas under the curves of the wheal-and-flare responses as a function of time (primary efficacy variables) were compared using analysis of variance. RESULTS: A highly significant overall treatment effect (P < .001) was detected for wheal and flare inhibition, with the activity of cetirizine and desloratadine significantly superior to that of placebo (P < .001). In addition, the activity of cetirizine was significantly superior to that of desloratadine (P < .001). With desloratadine, only 3 of the 18 subjects achieved a wheal inhibition of at least 70%, occurring between 2 and 4 hours, whereas all subjects using cetirizine reached a wheal inhibition of at least 70% between 0.5 and 3 hours (median time, 1.7 hours). The difference between the 2 active drugs was highly significant (P < .001). The median duration of wheal inhibition of at least 70% was zero with placebo and desloratadine and was 21.9 hours with cetirizine (P < .001). No serious adverse events were reported, and no subject withdrew from the study due to an adverse event. CONCLUSION: Cetirizine was associated with significantly greater suppression of skin reactivity to histamine compared with desloratadine during 24 hours after a single dose, with a consistent duration of action for cetirizine, as previously reported.     

The effects of butterbur on the histamine and allergen cutaneous response.

BACKGROUND: Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma. However, no data are available regarding its effects on the histamine and allergen cutaneous response. OBJECTIVE: To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses. METHODS: Atopic patients were randomized into a double-blind, double-dummy, crossover study to receive for 1 week butterbur, 50 mg twice daily (8 AM and 10 PM); fexofenadine, 180 mg once daily (10 PM), and placebo once daily (8 AM); montelukast, 10 mg once daily (10 PM), and placebo once daily (8 AM); or placebo twice daily (8 AM and 10 PM). Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine, allergen, and saline control at 10-minute intervals for 60 minutes. RESULTS: Twenty patients completed the study. The mean +/- SE histamine wheal and flare responses, respectively, were significantly attenuated (P < .05) by fexofenadine (9.4 +/- 1.8 mm2 and 13.5 +/- 3.2 mm2) compared with placebo (15.5 +/- 3.3 mm2 and 179.8 +/- 74.3 mm2) but not by butterbur (16.4 +/- 2.1 mm2 and 297.7 +/- 121.2 mm2) or montelukast (19 +/- 1.9 mm2 and 240.2 +/- 66.6 mm2). The allergen wheal and flare responses, respectively, were also significantly attenuated (P < .05) by fexofenadine (31.1 +/- 6.3 mm2 and 256.9 +/- 86.5 mm2) compared with placebo (65.4 +/- 15.2 mm2 and 1,014.5 +/- 250.0 mm2) but not by butterbur (50.4 +/- 9.2 mm2 and 1,110.3 +/- 256.1 mm2) or montelukast (58.8 +/- 9.1 mm2 and 1,463.6 +/- 295.6 mm2). CONCLUSIONS: Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo, whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation. This finding would suggest that butterbur may not be effective in allergic skin disease.     

Comparison of electrically induced flare response patterns in human and pig skin

Objective

We compared the characteristics of neurogenic flare responses in human and pig skin to establish a translational research animal model.

Material and subjects

Eight domestic pigs and six male subjects were investigated.

Treatment

Electrical pulses were delivered transcutaneously with increasing current intensities, pulse frequencies and pulse widths.

Methods

Inflammatory skin responses were recorded by laser Doppler imaging and analyzed by ANOVA and Fisher’s (LSD) post hoc test.

Results

Transcutaneous stimuli of 5 mA onward induced a significant flare development in humans. In the pig, significantly lower currents of 2.5 mA already induced a flare response. Smaller flare sizes of about 3.5 cm² were analyzed. The flare continuously declined despite ongoing stimulation.

Conclusions

Lower excitation thresholds and smaller receptive fields of nociceptors can be suggested in pigs. Impaired neuropeptide release, altered vesicle replenishment, different neuropeptide sensitivity, or insufficient peripheral decoding of action potentials may contribute to steadily decreasing flare responses. These attributes may be objectives of pre-clinical anti-hyperalgesic studies and their accurate analysis in pigs reveals a particularly sensitive translational animal model for nociceptor researches.     

Characteristics of tree nut challenges in tree nut allergic and tree nut sensitized individuals

Background

Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied.

Pathology of rituximab-induced Kaposi sarcoma flare

Background

Kaposi sarcoma (KS) flare may occur following therapy with corticosteroids, as part of the immune reconstitution inflammatory syndrome seen with highly active antiretroviral therapy (HAART), and after rituximab therapy. The exact mechanism responsible for iatrogenic KS flare is unclear.

Methods

A case of AIDS-associated cutaneous KS flare following rituximab therapy was compared to similar controls by means of immunohistochemistry using vascular makers (CD34, CD31), monoclonal antibodies to Human Herpesvirus 8 (HHV8) gene products (LNA-1, K5), as well as B-lymphocyte (CD20) and T-lymphocyte (CD3, CD4, CD8) markers.

Results

CD20+ B-cell depletion with rituximab in KS flare occurred concomitantly with activation of the HHV8 immediate early gene protein K5. KS flare in this patient was successfully treated with liposomal doxorubicin and valganciclovir.

Conclusion

Rituximab-induced KS flare appears to be related to HHV8 activation. Effective management of iatrogenic KS flare therefore depends upon the control of HHV8 viremia in conjunction with specific chemotherapy for KS.     

Comparison between skin prick test and serum immunoglobulin E by CAP system to inhalant allergens

Background

Skin prick tests (SPTs) and measurements of serum specific immunoglobulin E (sIgE) antibodies are the most commonly used diagnostic tools for confirming sensitization. However, disagreement between the tests has been observed.

A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers

BACKGROUND: Cetirizine is a highly efficacious and long-acting second-generation H1-receptor antagonist for the treatment of allergic diseases, such as allergic rhinitis and chronic idiopathic urticaria, in adults and children. Pharmacologic studies have demonstrated that cetirizine, a racemate mixture composed of equal amounts of two enantiomers, does not undergo hepatic metabolism to any significant level. The enantiomers are excreted mainly unchanged, predominantly in the urine and to a lesser extent in the faeces. METHODS: The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles. RESULTS: Both cetirizine and levocetirizine caused a marked inhibition of histamine-induced wheal and flare, whereas ucb 28557 was inactive in this model. Inhibition of the wheal response observed for cetirizine and levocetirizine was apparent by 1 h after dosage and lasted for mean durations of 24.4 and 28.4 h, respectively. In addition, the response for cetirizine and levocetirizine became maximal by 6 h after treatment, rising to 79.5% and 83.8%. Similarly, cetirizine and levocetirizine also markedly inhibited the histamine-induced flare response. This effect was evident for both drugs by 1 h after dosage and lasted over a mean period of 28.4 and 26.0 h, respectively, for cetirizine and levocetirizine. The inhibitory effect of these compounds on histamine-induced flare response was also maximal by approximately 6 h after dosage, peaking at 88.5%) and 83.6%, respectively. Statistical evaluation showed that cetirizine and levocetirizine were equivalent for maximum inhibition of histamine-induced wheal and flare. However, levocetirizine was found to be superior to cetirizine when area under the curve was compared. In contrast, ucb 28557 was not found to inhibit histamine-induced wheal and flare responses at any time during the study period. Plasma concentrations of levocetirizine were found to be approximately double those of ucb 28557 at 4 and 8 h after dosing, and 50-60% of the drugs were excreted unchanged in urine over a period of 32 h. CONCLUSIONS: The finding that, in this model, levocetirizine 2.5 mg has comparable antihistaminic activity to cetirizine 5 mg, whereas its other enantiomer ucb 28557 has no pharmacodynamic effect, suggests that the antihistaminic properties of cetirizine observed in the management of allergic skin conditions are likely to be attributable to levocetirizine.     

Levocetirizine better protects than desloratadine in a nasal provocation with allergen

BACKGROUND: Direct comparisons of antihistamines are rare but very much needed. Newly available antihistamine preparations, levocetirizine, the R-enantiomer of racemate cetirizine, and desloratadine, an active metabolite of loratadine, have been recently released for allergic rhinitis. OBJECTIVE: We sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen. METHODS: Twenty-four volunteers with grass pollen allergy and a history of rhinitis were enrolled in a double-blind, placebo-controlled, crossover study. Three NPTs were performed in a dose-escalating manner during the out-of-season period 4 hours after a single dose of levocetirizine (5 mg), desloratadine (5 mg), or placebo. RESULTS: CONCLUSIONS: This study demonstrates a better overall protection of a single dose of levocetirizine compared with desloratadine in an NPT with grass pollen allergen. In contrast to late-phase inflammatory markers, which were unaffected, extravascular leakage of the early-phase marker albumin was significantly limited by levocetirizine.     

A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine-induced skin reactivity

OBJECTIVE: The aim of this double-blind, randomized, crossover, placebo-controlled clinical trial was to compare the inhibition of the histamine-induced skin reaction induced by ebastine 20 mg with respect to that induced by fexofenadine 120 mg or placebo. METHODS: Eighteen volunteers (10 males, 8 females) received the three treatments once daily for 5 days, with a mean 7-day washout period between treatments. Intradermal tests, using 0.05 ml from a solution containing 100 microg/ml of histamine, were performed at baseline and at 1, 1.5, 2, 3, 10 and 24 h after a single dose and repeated 5-day dose, and in addition after 34, 48, 58 and 72 h after repeated 5-day dose. RESULTS: After 24 h of acute administration, ebastine 20 mg was significantly more effective than fexofenadine 120 mg in reducing the wheal and flare induced by histamine challenge (p<0.001). Although fexofenadine 120 mg had the shortest onset of action (1.5 vs. 3 h in ebastine 20 mg), the duration of its antihistamine effect was the shortest (24 vs. 58 h in ebastine 20 mg) and wheal reduction after 24 h was not significantly different from placebo. The overall effect after single and repeated 5-day dose, expressed as the AUC of reduction of wheal and flare area (%/h), showed the following order of magnitude: ebastine 20 mg>fexofenadine 120 mg>placebo. No significant differences in the incidence of adverse events were found between the three treatments. CONCLUSIONS: The present results clearly show a superior and long-acting effect of ebastine 20 mg compared with fexofenadine 120 mg on the skin response to histamine 24 h after dosing.     

H1‐antihistamines and urticaria: how can we predict the best drug for our patient?

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H₁‐antihistamines currently available and the pharmaceutical industries need to keep developing H₁‐antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head‐to‐head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H₁‐antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H₁‐antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine‐induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.     

Comparison of the effects in the nose and skin of a single dose of desloratadine and levocetirizine over 24 hours

BACKGROUND: Desloratadine (DL) and levocetirizine (LCZ) are the newest commercialized antihistamines. Pharmacokinetics, pharmacodynamics and clinical data are available for both drugs, but there is to date no direct comparison involving the nose and skin at the same time. We compared the effects of a single dose of the two drugs in the nose and skin over 24 h. METHODS: Twenty-three patients with symptomatic allergic rhinitis were enrolled in a randomized double-blind crossover administration of DL and LCZ. The histamine-induced wheal and flare was measured at baseline and 2 and 24 h after dosing. A reflective total symptom score (rTSS) for the previous 24 h was assessed before and after each dose. An instant symptom score was also measured at various time points after each drug. RESULTS: LCZ provided greater inhibition of the flare at 2 h (p = 0.05) and at 24 h (p = 0.007) and greater inhibition of the wheal only at 2 h (p = 0.02). The decrease in wheal and flare was significant versus baseline (p = 0.007) with both drugs. The rTSS of the previous 24 h decreased significantly with both LCZ (11.53 vs. 8.0; p < 0.05) and DL (11.3 vs. 7.9; p < 0.05). The instant TSS progressively decreased in parallel with both drugs, but a difference in favor of LCZ was seen 2 h after dosing. CONCLUSIONS: Single doses of DL and LCZ had a comparable effect on nasal symptoms, but LCZ was faster and displayed a greater effect on histamine wheal.     

Randomized placebo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria

BACKGROUND: H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus, and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria (CIU). Recently, antileukotriene receptors have been used in patients with CIU, either administered as monotherapy or combined with H 1 -receptor antagonists. OBJECTIVE: We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist, 10 mg of montelukast daily, and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo. METHODS: One hundred sixty patients aged 18 to 69 years (mean +/- SD, 43.9 +/- 13.4 years) with a history of moderate CIU were selected. A randomized, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Patients were treated with 5 mg of desloratadine once daily (n = 40), 10 mg of montelukast once daily (n = 40), 5 mg of desloratadine (n = 40) in the morning plus montelukast in the evening, or matched placebo (n = 40). Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously. RESULTS: Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study. Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment. As reflective evaluation, all groups showed significant differences compared with the placebo group in terms of total symptom score, number of hives, and size of largest hive. In addition to the pruritus, only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo, whereas there were no differences between the montelukast and placebo groups. Finally, no differences were found between the desloratadine group and the desloratadine plus montelukast group. The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group, whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive. No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group. CONCLUSIONS: The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU. In addition, the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU.     

The effects of various doses of bacterial lipopolysaccharide on the expression of CD63 and the release of histamine by basophils of atopic and non-atopic patients

Objective

We tested the effect of various doses of bacterial lipopolysaccharide (LPS, endotoxin) on the expression of CD63 and the in vitro release of histamine by basophils stimulated with ragweed allergen in patients with or without ragweed and mite allergies.

Methods

The peripheral blood of 11 patients with ragweed allergy, 10 patients with mite allergy and 14 control patients was incubated with ragweed allergen extract following pretreatment with varying doses of LPS. The expression of CD63 in basophils was measured by flow cytometry, and the release of histamine was determined by ELISA.

Results

In the samples of patients with ragweed allergy that were exposed to specific allergen, only high doses of LPS significantly elevated the expression of CD63 (200 ng/ml; 1,000 EU/ml) and the release of histamine (2,000 ng/ml; 10,000 EU/ml). There was no effect of LPS in any other cases.

Conclusions

Bacterial LPS (endotoxin) concentrations higher than 200 ng/ml (1,000 EU/ml), which rarely occurs in nature, could only activate the basophils from atopic patients whilst in the presence of the specific allergen. Thus, the restoration of the urban, “microbe-poor” milieu with endotoxin (as LPS) can be a promising and harmless approach for allergy prevention.     

Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial

Background

Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT.

Methods

This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD?+?HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT.

Results

Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD?+?HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD?+?HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD?+?HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P?=?0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD?+?HDM/SCT group and 69.4% in the HDM/SCT alone group (P?=?0.03).

Conclusions

Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone.

Trial registration

This trial has been registered at clinicaltrials.gov with the number NCT01998503.     

Diagnosis and Immunotherapy of Mould Allergy

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children

BACKGROUND: Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE: We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS: A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS: Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION: In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS: The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.