Clinical assessment of tolerability, immunological and cutaneous reactivity effects of an abbreviated schedule with Olea europaeanative extract of subcutaneous immunotherapy.

Summary: Objectives. To evaluate the tolerability and efficacy of Olea europaea subcutaneous immunotherapy (SCIT) on patients with rhinoconjunctivitis. Methods. In this open clinical trial patients were assigned to an abbreviated build-up scheme. The outcomes were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Results. Only 8 systemic reactions were registered, which represented 7/47 (14.9%) of patients and 8/429 (1.9%) of administered doses. Regarding immunological parameters the significant increases of sIgG and sIgG4 evidenced the changes in the patient immune system. Cutaneous reactivity decreased significantly. Conclusions. Olea europaea SCIT (Allergovac® depot ROXALL Medicina España S.A.) showed a good safety and tolerability profile. Immunological changes with induction of blocking IgG and decreases in cutaneous reactivity were detected in the patients.

Occupational respiratory allergy in peach crop workers.

BACKGROUND: Occupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees. METHODS: Prick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE-immunoblotting with patient sera and rabbit serum anti-Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract. RESULTS: Most patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE-immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16-kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested. CONCLUSIONS: Sensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE-binding proteins matching LTP and/or profilin.

Renal amyloidosis in a patient with X-linked agammaglobulinemia (Bruton's disease) and bronchiectasis.

PURPOSE: We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis. CASE REPORT: A 38 year-old man was diagnosed with X-linked agammaglobulinemia (Bruton's disease) when he was 3 years old, and he has been treated with parenteral immunoglobulin since then. Eighteen years later, he was diagnosed with central pulmonary bronchiectasis by computerized tomography (CT). In 2008, he gradually developed anemia, edema of lower limbs, and loss of weight. METHOD AND RESULTS: Laboratory studies revealed deterioration of renal function, normocytic normochromic anemia and nephrotic range proteinuria. Hepatitis B and C and HIV serology were negative. Ultrasound and CT of abdomen were normal. A renal biopsy revealed deposits with positive PAS and Congo red staining in glomeruli, interstitium, and vessel's walls. Immunohistochemistry showed positive staining of the A amyloid. Direct immunofluorescence was positive with thioflavin and showed focal and glomerular mesangial IgG deposits, suggesting renal AA amyloidosis. For 2 years the patient conducted pharmacological treatment and follow-up for the Nephrology department with poor prognosis and progression of renal function impairment. In January 2011 he began dialysis treatment with improvement, and he is currently on the waiting list for renal transplantation. CONCLUSION: We present a patient with Bruton's disease and bronchiectasis who developed renal AA amyloidosis a finding rarely reported.

General trends in airborne pollen production and pollination periods at a Mediterranean site (Badajoz, southwest Spain).

BACKGROUND: The aim of this study was to determine trends in the airborne pollen concentration and pollination period for the principal sources of pollen in Badajoz (southwest Spain) over 15 years of monitoring (1994-2008). METHODS: Airborne pollen was monitored by continuous sampling with a Hirst volumetric sampler. Pollen trends were investigated by linear regression and correlation analysis using mean annual and monthly pollen concentrations. The aerobiological results were compared with meteorological data (temperature and rainfall). RESULTS: During the study period, the mean total annual rainfall was 66.2 mm lower than normal and the mean annual temperature 0.8 degrees C higher than normal. No temporal trend was found for total airborne pollen concentration, but differences were observed for monthly data, namely, an increase in January, February, and May and a decrease in March and June. For the different pollen types studied, there was a general trend toward increased values in the month with the highest values, and this trend seemed to be related to temperature.The beginning of the main pollen season occurred later, and the end occurred sooner; therefore, the main pollen season seems to be shorter. CONCLUSIONS: Our data reflect trends in the response of plants to changing rainfall stress patterns in Mediterranean countries, and these trends seem to be different from those of temperate countries. Nonetheless, a longer study period will be required to confirm these preliminary conclusions.

Recurrent angioedema due to lysozyme allergy.

A 54-year-old woman suffered an episode of dyspnea and edema affecting her eyelids, tongue, and lips a few minutes after intake of Lizipaina (bacitracin, papain, and lysozyme). She was treated with intravenous drugs and her symptoms improved within 2 hours. She had experienced 3 to 4 bouts of similar symptoms related to the ingestion of cured cheeses or raw egg. Specific serum immunoglobulin (Ig) E against lysozyme was present at a concentration of 0.45 kU/L, and no specific IgE was found against egg white and yolk, ovalbumin, or ovomucoid. Skin prick tests were positive with commercial extracts of egg white and lysozyme but doubtful with yolk, ovalbumin, and ovomucoid. Prick-to-prick tests with raw egg white and yolk gave positive results, but negative results were obtained with cooked egg white and yolk and 5 brands of cheese (3 of them containing lysozyme and the other 2 without lysozyme). Controlled oral administration of papain, bacitracin, and cheeses without lysozyme was well tolerated. We suggest that the presence of lysozyme in a pharmaceutical preparation, cured cheese, and raw egg was responsible for the symptoms suffered by our patient, probably through an IgE-mediated mechanism.

Severe immediate reaction to nabumetone.

Nabumetone is a nonsteroidal antiinflammatory (NSAID) prodrug that inhibits cyclooxygenase-2. It has been recommended as a safe alternative in most patients with hypersensitivity reactions to NSAIDs. Systemic reactions caused by nabumetone are not frequent. We report 2 cases of immediate systemic reactions due to nabumetone. The first case involved a 68-year-old woman who developed immediate generalized pruritus, erythema, morbilliform eruption, swollen tongue sensation, diarrhea, and hypotension after the ingestion of a single dose of nabumetone. In the second case, a 77-year-old woman developed generalized pruritus, palm erythema, colic abdominal pain, diarrhea, dizziness, tightness of the chest, dyspnea, and hypotension immediately after oral intake of nabumetone. Both patients had previously tolerated this drug. Since these episodes, they have avoided nabumetone. Skin prick tests with nabumetone (10 and 100 mg/mL) were negative. Oral challenge tests with other NSAIDs, even of the same group as nabumetone, were negative in both patients. The mechanisms responsible for the reaction were not established.

Hypersensitivity reaction to mizolastine: study of cross reactions.

A 26-year-old male suffering from acute rhinitis took the first dose of Zolistan (mizolastine, 10 mg), orally, and 15 minutes later he developed intense generalized pruritus, cutaneous rash, oropharyngeal pruritus, edema on his face, difficulty in swallowing, and mild dyspnea. He was treated with methylprednisolone and epinephrine and improved within 30 minutes. The patient had not taken mizolastine before and he has avoided it since the reaction. Cutaneous tests with Zolistan and its excipients proved negative. Simple-blind oral challenge tests with the excipients and then with Zolistan were positive only with Zolistan. In order to confirm the absence of cross-reactivity between mizolastine and other benzimidazoles, we tested omeprazole, domperidone and mebendazole, all of which yielded negative results. To our knowledge, this is the second case of immediate hypersensitivity to mizolastine documented to date. In our case, the clinical history, physical examination and provocation tests allow us to establish the diagnosis of hypersensitivity to mizolastine and exclude the cross reactivity with other benzimidazole derivatives.

Ibuprofen-induced fever in Sjogren's syndrome.

A 68-year-old woman with a medical history significant for Sjögren syndrome and leukocytoclastic vasculitis of small vessels presented to the emergency department with chills, malaise, a temperature of 39 degrees C, nausea, vomiting, and hypotension. Fifteen minutes earlier she had taken ibuprofen for flu-like symptoms. She was treated with a perfusion of intravenous saline, paracetamol, and ciprofloxacin with improvement 24 hours later. Three months later, she had a similar episode, without hypotension. An oral challenge test with ibuprofen in the hospital produced the same symptoms 3 hours after the last dose. She was treated with metamizole and paracetamol and was asymptomatic the next day. This is the first report of a febrile reaction to ibuprofen in a patient with Sjogren's syndrome.

Erythroderma due to aztreonam and clindamycin.

A 73-year-old woman developed erythroderma with intense pruritus, malaise, and chills 7 days after treatment with intravenous clindamycin. Two years later she experienced a similar reaction with more rapid onset (48 hours) after treatment with aztreonam. Resolution followed withdrawal of treatment in both instances, and intradermal tests proved positive at delayed reading for both drugs.

Patch tests for diagnosis of delayed hypersensitivity to cephalosporins.

BACKGROUND: Few studies have reported delayed hypersensitivity reactions to systemically administered cephalosporins. The diagnostic procedures and extracts for these reactions are not standardized, and little is known about the extent of cross reactivity among different cephalosporins. CASES REPORT: We report 2 cases of delayed hypersensitivity reactions due to cephalosporins presenting as erythrodermia. Case 1. An 80-year-old man developed generalized pruritus and erythema 2-3 days after starting treatment with cefuroxime. The drug was stopped and antihistamines and corticosteroids were administered. The patient improved 5-6 days later, and mild superficial desquamation was observed. Case 2. A 66-year-old woman experienced similar symptoms 4-5 days after beginning cefazolin. She reported a similar reaction with ceftazidime 8 years previously. METHODS AND RESULTS: Skin prick tests and specific IgE against penicillin G and V, amoxicillin, ampicillin and cephalosporins were negative. Intradermal tests with ceftazidime and cefazolin were positive in case 2 at delayed reading. Patch tests using benzylpenicillin, ampicillin, amoxicillin, several cephalosporins, aztreonam and imipenem were positive to all the cephalosporins tested (at 48 and 96 hours) and were negative to the other betalactams. Controlled administration of amoxicillin, benzylpenicillin, aztreonam and imipenem was well tolerated by both patients. CONCLUSIONS: 1) We report 2 cases of delayed hypersensitivity reactions due to cephalosporins presenting as erythrodermia. 2) Epicutaneous tests were useful for diagnosis. 3) Both patients tested positive to all cephalosporins and negative to other betalactams.

Cutaneous reactions due to diltiazem and cross reactivity with other calcium channel blockers.

BACKGROUND: The spectrum of cutaneous eruptions in association with calcium channel blockers is extensive, varying from exanthemas to severe adverse events. Reactions due to diltiazem occur more frequently than with other calcium channel blockers. Patch testing has been used as confirmatory testing in patients with extensive cutaneous reactions. Cross-reactivity among these drugs have not been established. MATERIAL: We present 3 patients: 1) A 54-year-old man developed a generalized erythema-multiforme-like reaction followed by erythrodermia and exfoliative dermatitis 6-7 days after starting on diltiazem. The drug was stopped and remission was obtained with emollients and systemic corticosteroids and antihistamines within 12 days. 2) A 80-year-old woman experienced a pruritic exanthematous eruption on her trunk which evolved to generalized erythrodermia and superficial desquamation. This reaction appeared 10 days after taking diltiazem, and gradually improved in 10-12 days after discontinuation of this drug. 3) A 79-year-old man presented with erythema and pruritus initially on the back, and then affecting thorax, extremities and face. He had started treatment with diltiazem three days before. Diltiazem was stopped and steroid and antihistamine therapy was given. His skin condition improved, but 3 days later the patient received verapamil with worsening of previous situation. He recovered within 7 days. METHODS AND RESULTS: Two to six months after the reaction, we carried out epicutaneous tests with calcium channel blockers from different groups. Diltiazem proved positive (at 48 and 96 hours) in the three patients; nifedipine was also positive in patient 2, and verapamil in patient 3. Controlled administration of verapamil was well tolerated in patient 2 after the reaction, and the patient 1 has taken nifedipine without problems. CONCLUSIONS: 1) We report 3 cases of cutaneous reactions due to diltiazem. 2) Epicutaneous tests have been useful for diagnosis. 3) As one of patients had positive patch tests to diltiazem and nifedipine, and other one with diltiazem and verapamil, more studies are needed to demonstrate cross reactions among calcium channel blockers.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Cheilitis granulomatosa of Melkersson-Rosenthal syndrome: treatment with intralesional corticosteroid injections.

BACKGROUND: Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent. The available therapeutic options provide only limited success or temporary benefit. CASE REPORT: A 20-year-old man presented with a 7-month history of recurrent episodes of swelling of the upper lip without pain, burning or local pruritus. No causative factors, such as food, drugs or latex, or physical, chemical or emotional conditions could be identified. The patient had been treated with oral antihistamines and corticosteroids with no clinical improvement. Physical examination showed firm edema without fovea, limited to the central area of the upper lip without epidermal changes or symptoms on palpation. The patient had a previous history of facial palsy 6 years previously and recurrent episodes of herpes simplex labialis. Skin prick tests with inhalant aeroallergens, food, latex and Anisakis allergens were negative. Laboratory investigation revealed normal complete blood count, erythrocyte sedimentation rate, thyroid hormones, biochemistry, complement components (C3, C4 and C1-esterase inhibitor) and CH50, rheumatoid factor, antinuclear antibodies, immune complexes, protein electrophoresis and immunoglobulins. Thorax and paranasal sinus radiographs were clear. Biopsy of the involved area of the lip showed edema with lymphocytic and plasma cell infiltration and mononuclear perivascular infiltrates without granulomas, suggesting initial granulomatous cheilitis. Because the patient showed lack of response and/or poor tolerance to prior treatments (deflazacort, clofazimine and metronidazole), intralesional triamcinolone injections were administered with satisfactory response from the first session. CONCLUSIONS: Response to available treatments for Melkersson-Rosenthal syndrome is highly variable. In the present case, intralesional triamcinolone injections were effective.