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עמוד בית
Sun, 20.07.25

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January 2012
Mauro Calvani, MD, Iride Dello Iacono, MD, Valentina Giorgio, MD, Stefano Miceli Sopo, Valentina Panetta, MD and Salvatore Tripodi, MD.

Background: The diagnostic gold standard for food allergy is an oral food challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset of mild objective symptoms for fear of severe reactions. However, there is no consensus on this issue.

Objective: To investigate the effectiveness and side effects of a new model of oral milk challenge in order to increase the diagnostic accuracy of cow¡¯s milk protein allergy and reduce the number of many useless elimination diets. This model is characterized by a conservative diagnostic protocol and ¡°step-up cow’s milk administered dosing.¡± The secondary aim was to investigate possible factors influencing severe reactions.   

Methods: Sixty-six children (median age 1 year, range 1¨C18) with suspected immunoglobulin E (IgE)-mediated cow’s milk allergy performed a conservative oral food challenge (OFC), i.e., the OFC was continued even in the presence of subjective, even repeated, or mild local or multiple organ objective symptoms. If the first objective reaction occurred when the quantity of milk was > 10 ml, the investigator would decide whether to continue the OFC or prescribe a gradual increase in milk feeding at home.

Results: Symptoms developed during the OFC in 42.4% of the children. Local, generalized and severe generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children, respectively. Only 14/28 (50%) who developed objective symptoms during the OFC were considered to be affected by cow’s milk allergy. In the remaining 14 both subjective and objective symptoms developed and the OFC was continued without the emergence of additional symptoms. Epinephrine was administered to 6 of the 28 children (21.4%) who developed objective symptoms. All but one had subjective symptoms following the early doses of milk, whereas all children who later tolerated milk had their first subjective or mild symptoms following doses ¡Ý 10 ml.

Conclusions: This new model of oral milk challenge criteria led to frequent severe allergic reactions hence its use in daily practice seems inadvisable. However, our study provides evidence that a severe allergic reaction does not invariably occur if the offending food continues to be administered after the onset of symptoms. If mild symptoms appear at doses higher than 10 ml, continued milk administration, on the same day or in subsequent days, seems to facilitate the development of tolerance and may reduce the number of useless elimination diets.


Antonella Cianferoni, MD, PhD, Jackie P. Garrett, MD, David R. Naimi, MD, Karishma Khullar, BS and Jonathan M. Spergel, MD, PhD.

Background: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE) and clinical history have limited value individually in predicting the severity of outcome of the oral food challenge (OFC). 

Objectives: To develop a score that accounts for SPT, sIgE and clinical history to predict the risk of severe reaction to the OFC. 

Methods: A 5 year retrospective chart review was performed on 983 children who underwent OFC to egg, milk and peanut. 

Results: Using multilogistic regression, four major indicators were found to be independently associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001) , wheal size of the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P < 0.01)  and three were independently associated with anaphylaxis: wheal size (OR = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P < 0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0–4) was developed which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction, and age. A score of 0–1 had a negative predictive value for multisystem reaction to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3–4 had a positive predictive value for anaphylaxis:  62% for milk, 92% for egg and 86% for peanut.

Conclusions: Severe reaction to milk, egg and peanut OFC can be predicted using a simple score that takes into account clinical data that are commonly available prior to the challenges.

Silvia Sanchez-Garcia, MD, Pablo Rodriguez del Rio, MD, Carmelo Escudero, MD, Cristina Garcia-Fernandez, MD, Antonio Ramirez, MD and M.D. Ibanez, MD, PhD

Background: In the last two decades milk oral immunotherapy has gained interest as an effective treatment option for milk-allergic patients.

Objectives: To report on the efficacy of a milk oral immunotherapy.

Methods: Children with immunoglobulin E-mediated cow’s milk allergy were included in the protocol. The treatment consisted of an induction phase in which milk doses were increased weekly in the hospital, while the tolerated dose was continued daily at home. The goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance phase, patients ingested at least 200 ml of milk in a single dose every day.

Results: The protocol was applied to 105 milk-allergic children diagnosed by specific IgE to milk and controlled oral food challenge. The mean duration of the induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully complied with the protocol and 19 (19.1%) failed. Causes of failure were moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7 (6.66%). A total of 182 adverse reactions occurred during the induction phase, most of them mild. Baseline specific IgE to milk and casein were significantly lower (P < 0.05) in the successfully treated group compared to the group in which the treatment failed.

Conclusions: Milk oral immunotherapy is a safe and effective treatment for milk-allergic children, although adverse reactions may occur. Baseline milk and casein-specific IgE may be useful to predict a good response to milk oral immunotherapy.

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[1] IgE = immunoglobulin E

Giuseppe Crisafulli, PhD, Lucia Caminiti, MD and Giovanni B. Pajno, MD
May 2010
D. Miron, Y. Horovitz, A. Luder, F.S. Ohnona and Y. Schelisinger

Background: Human parvovirus B19 is a global and common infectious pathogen in humans, primarily in children.

Objectives: To assess the immunoglobulin G seroprevalence of B19 in children in Israel.

Methods: Overall, 128 previously healthy children (1.5–17 years old) hospitalized for various diseases other than acute human parvovirus B19 infection were assessed for IgG[1] to the virus by enzyme-linked immunosorbent assay. 

Results: The IgG seroprevalence increased from 22% in children aged 1.5–9 years to 52% in older children (P = 0.001).

Conclusions: Our data suggest that most acute parvovirus B19 infections in Israel occur in the early school years, and that by 18 years of age 50% of Israeli children have been infected by the virus.


[1] IgG = immunoglobulin G

December 2008
M. Rottem, D. Shostak, S. Foldi

Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.

Objectives: To examine the relation between CmsIgE[1] and the probability of resolution of milk allergy.

Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.

Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.

Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.

 






[1] CmsIgE = cow’s milk-specific immunoglobulin E


January 2008
Y. Shoenfeld, M. Blank, M. Abu-Shakra, H. Amital, O. Barzilai, Y. Berkun, N. Bizzaro, B. Gilburd, G. Zandman-Goddard, U. Katz, I. Krause, P. Langevitz, I.R. Mackay, H. Orbach, M. Ram, Y. Sherer, E. Toubi and M.E. Gershwin
Y. Sherer, S. Kuechler, J. Jose Scali, J. Rovensky, Y. Levy, G. Zandman-Goddard and Y. Shoenfeld

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.






[1] SLE = systemic lupus erythematosus

[2] IVIg = intravenous immunoglobulin


S. Fuchs, T. Feferman, R. Meidler, T. Brenner, O. Laub and M.C. Souroujon

Backgraound: Intravenous immunoglobulin administration has been beneficially used for the treatment of a variety of autoimmune diseases including myasthenia gravis, although its mode of action and active components have not yet been fully identified.

Objectives: To isolate from IVIg[1] a disease-specific fraction involved in the therapeutic activity in myasthenia and to identify its properties and function.

Results: IVIg administration in experimental autoimmune MG[2] results in suppression of disease that is accompanied by decreased Th1 cell and B cell proliferation. Chromatography of IVIg on columns of IgG from rats with EAMG[3] or from MG patients resulted in depletion of the suppressive activity that IVIg has on rat EAMG. Moreover, the minute amounts of IgG fractions eluted from the EAMG or MG-specific columns retained the immunosuppressive activity of IVIg.

Conclusions: Our study supports the notion that the therapeutic effect of IVIg is mediated by a minor disease-specific immunoglobulin fraction that is present in IVIg and is essential for its therapeutic activity.





[1] IVIg = inravenous immunoglobulin

[2] MG = myasthenia gravis

[3] EAMG = experimental autoimmune myasthenia gravis 


L. Guillevin and C. Pagnoux

Treatment of vasculitides has progressed markedly over the past few decades. Recent therapeutic strategies in severe and refractory anti-neutrophil cytoplasmic antibodies-associated vasculitides include immunomodulating methods (e.g., plasma exchanges), products (such as intravenous immunoglobulins) and, more recently, new agents called biotherapies. Some of them (e.g., anti-tumor necrosis factor-alpha and anti-CD20 monoclonal antibodies) have achieved promising results and are now often used to treat severe cases.

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