Mastocytosis: the safety of different COVID-19 vaccines / Mastocitose: segurança de diferentes vacinas contra a COVID-19

The COVID-19 pandemic has forced the development of vaccines to fight SARS-CoV-2. After vaccination began, reports of adverse reactions, including anaphylaxis, emerged. This raised concerns about the safety of COVID-19 vaccines in patients diagnosed with mastocytosis. The authors share their experience in administering different COVID-19 vaccines to patients diagnosed with mastocytosis.

A pandemia por COVID-19 obrigou ao rápido desenvolvimento de vacinas para combate ao SARS-CoV-2. Após o início da vacinação começaram a surgir relatos de reações adversas às vacinas, incluindo reações anafiláticas, surgindo dúvidas sobre a segurança das vacinas em doentes com mastocitose. Os autores apresentam a sua experiência em relação à administração de diferentes vacinas contra a COVID-19 em doentes com diagnóstico de mastocitose.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease resulting from loss-of-function pathogenic variants in ADA2 gene, which might resemble polyarteritis nodosa (PAN). The authors present two pediatric cases of ADA2 deficiency with phenotypic manifestations of PAN, including an unusual presentation with spinal cord ischemia. Also described is an assessment of ADA2 activity and gene expression profiling with description of a previously unreported homozygous variant, c.1226C > A (p.(Pro409His)), detected in a patient with consanguineous parents, confirmed by near-absent ADA2 plasma enzymatic activity. The authors suggest to first obtain enzymatic activity, whenever DADA2 is suspected, before proceeding to genetic testing, due to its excellent cost-effective results. Moreover, physicians must be aware of this monogenic disorder, especially in the case of early-onset PAN-like manifestations, having a family member with similar manifestations or having consanguineous parents suggesting an autosomal recessive inheritance pattern. Given the multi-organ involvement, recognizing the diverse manifestations is a crucial step towards timely diagnosis and management of this potentially fatal but often treatable syndrome.

Subcutaneous immunotherapy induces alterations in monocytes and dendritic cells homeostasis in allergic rhinitis patients.

BACKGROUND: Specific subcutaneous immunotherapy (SCIT) can achieve long-term remission in patients with allergic rhinitis (AR) through complex and still unknown mechanisms. The aim of this study is to evaluate the effect of SCIT over CD16+ and CD16- monocytes, myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) in patients with AR, comparatively to pharmacological standard treatment (non-SIT). METHODS: The relative frequency and absolute number of monocytes and DC subsets, the frequency of these cells producing TNFα after in vitro stimulation with Dermatophagoides pteronyssinus (Dpt) extract, and the expression levels of receptor-bound IgE or IgG were assessed by flow cytometry, in peripheral blood samples from 23 healthy individuals (HG) and 43 participants with AR mono-sensitized to Dpt; 10 with non-SIT treatment and 33 under SCIT, just before (SCIT-T0) and 4 h after administration (SCIT-T4). Moreover, IFNα mRNA expression was evaluated in purified pDCs, by qRT-PCR. RESULTS: After SCIT administration we observed a strong decrease of circulating pDCs, although accompanied by higher levels of IFNα mRNA expression, and an increase of circulating CD16+ monocytes. AR participants under SCIT exhibited a higher expression of receptor-bound IgE in all cell populations that expressed the high affinity receptor for IgE (FcεRI) and a higher frequency of CD16+ monocytes producing TNFα. Conversely, we observed a decrease in the frequency of mDCs producing TNFα in AR under SCIT, similar to the observed in the control group. CONCLUSIONS: SCIT seems to induce numeric, phenotypic, and functional changes in circulating monocytes and dendritic cells, contributing at least in part to the well described immunological alterations induced by this type of immunotherapy.

Alterations on peripheral blood B cell subsets induced by allergic rhinitis.

OBJECTIVES AND DESIGN: Here we evaluated whether allergic rhinitis to Dermatophagoides pteronyssinus induces alterations on circulating B cell subsets. MATERIALS AND METHODS: Circulating B cell subsets and isotype expression on antigen-experienced B cells from allergic patients under conventional pharmacological treatment (NO-SIT, n = 15) and under subcutaneous immunotherapy (SCIT, n = 33), and non-allergic subjects (NC, n = 25) were analyzed by flow cytometry. RESULTS: In allergic patients, we found a significant decrease in IgM(+) and IgG(+) memory B cells and an increase in IgA(+) memory B cells. Additionally, the numbers of circulating IgA(+) plasmablasts in allergic patients were also increased, while those cells expressing IgM were reduced. CONCLUSIONS: Allergic patients have a disturbed B cell subsets distribution which seems to underlie rhinitis pathogenesis and remain unchanged after SCIT.

Impact of allergic rhinitis and specific subcutaneous immunotherapy on peripheral blood basophils of patients sensitized to Dermatophagoides pteronyssinus.

BACKGROUND: Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E - mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known. METHODS: Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/ß1 (TPSAB1) gene expression was assessed by real-time PCR. RESULTS: Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4. CONCLUSION: PB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.

Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: a case report.

INTRODUCTION: Food allergy is an increasing problem with limited therapeutic approaches apart from to the eviction diet. CASE PRESENTATION: A 40-year-old female patient with food allergy symptoms was polysensitized to almost all vegetable food since the age of 36; the onset of symptoms was during pregnancy. The allergological study demonstrated positive skin prick tests (SPT) to nuts, legumes, cereals, spices, several fresh fruits including peach, and other groups of vegetable foods however, it was negative to common aeroallergens. Serum specific IgE levels were negative (<0.35 kU/L) to profilin and carbohydrate determinants, but positive to Pru p 3 (3.5 kU/L). Positive double-blind placebo-controlled food challenge to peach confirmed the allergic disease. She received specific sublingual immunotherapy with native Pru p 3 at a concentration of 40 mug/ml with 5 administrations per week and a cumulative dose of 200 mug of nPru p 3 per month. After an ultra-rush build-up phase concluded in one day she continued therapy during a year with 5 administrations per week. The clinical evolution and laboratory studies demonstrated an early reduction on SPT reactions with no relevant changes on serum specific IgE, IgG, IgG(1) and IgG(4) to Pru p 3 during the immunotherapy period. The challenge test was negative 4 months after the beginning of the SLIT. Regarding clinical response she markedly improved after the first month of treatment, and by the 3th month she had no major vegetable dietary restrictions, except for nuts and pepper. CONCLUSION: These results demonstrate the excellent efficacy and safety of sublingual specific protein immunotherapy developed according to the patient specific sensitivity profile to Pru p3.

Dynamics of CD86 expression on allergic inflammation--new insights.

CD86 is a well-known costimulatory molecule in its interaction with CD28 and/or CTLA present on T cells, and is essential for full activation of naïve T-cell and subsequent differentiation. Usually the B7 molecules are expressed mainly on APCs and B cells and in specific conditions on other activated cells. These costimulatory molecules are involved in the development of allergic inflammation and airways hyperreactivity (AHR) in allergen-challenged mice. Activated T cells, CD4(+)CD25(+), express CD86 in the first 60 minutes after the specific inhalatory exposure. These T cells can be relevant in IgE mediated allergic reaction possibly by an autocrine costimulation via CD28/CTLA activation pathway. The blockage of the expression of CD86 could be a potential therapeutical target to reduce the magnitude or the progression of the allergic reaction. The review article also discussed relevant patents.

Sensitization to profilin in the Central region of Portugal.

BACKGROUND: Profilin is a panallergen found in pollens and fruits. Sensitization to this protein may explain some sensitization to multiple pollen species. We aimed to evaluate sensitization to profilin in patients suffering from respiratory allergy sensitized to pollens, in the Central region of Portugal. METHODS: Patients were evaluated for asthma symptoms, rhinitis, conjunctivitis and food allergy. Skin prick tests (SPT) to aeroallergens including 12 different pollens and profilin (nPho d 2) were performed. The patients were divided into two study groups according to the region of residence: A--inland region and B--coastal region. RESULTS: A total of 370 patients were evaluated (277-group A; 93-group B). 65.9% showed positive skin prick tests and 76.2% were positive to pollens (87.1%-group A; 42.85%-group B; p<0.0001). All the patients sensitized to pollens had rhinitis (p=0.001). Sensitization to profilin was associated with pollen sensitization (p=0.014). 43 patients were sensitized to profilin (40-group A; 3-group B; p=0.006). 21.0% of patients sensitized to pollens, were also sensitized to profilin. 39 patients were sensitized to at least two pollens (p<0.0001). Four profilin and pollen sensitized patients had oral allergy syndrome complaints to melon. This syndrome was related with profilin sensitization (p=0.001). CONCLUSIONS: It is advisable to perform SPT to profilin, particularly in the Inland region, for a better differential diagnosis between cross-reactivity and true sensitization to pollens. The results together with the medical history may support the choice for a specific immunotherapy option.

Effect of Dermatophagoides specific immunotherapy on cutaneous reactivity.

BACKGROUND: There are several immunological and clinical effects induced by specific immunotherapy (SIT). A reduction of reactivity to allergen is the final propose of this therapy. The aim of this study was to evaluate the specific cutaneous reactivity, two years after beginning SIT. METHODS: We included 95 patients with bronchial asthma (BA) and/or allergic rhinitis (AR) to house dust mites (HDM). 74 patients were submitted to subcutaneous SIT with commercial extracts of Dermatophagoides. The control group included the 21 patients without SIT. After a two years period, the cutaneous reactivity was reassessed, by skin prick tests (SPT). The effect of SIT in the cutaneous response was evaluated by calculating the difference between the wheal diameter of the SPT before and after treatment. A positive difference indicated a cutaneous reactivity reduction. RESULTS: The patients submitted to SIT included 52.7% males and 47.3% females, with a mean age of 18.4 +/- 13.9 years old. The cutaneous reactivity to D. pteronyssinus, before and two years after the beginning of SIT, were 6.9 +/- 3 mm and 5.1 +/- 2.9 mm, respectively, with 1.87 of difference (p = 0.0001). The cutaneous reactivity to D. farinae, before and two years after the beginning of SIT, were 6.2 +/- 2.4 mm and 5.0 +/- 3.7 mm, respectively, with 0.93 of difference (p = 0.0790). In the control group, the cutaneous reactivity to D. pteronyssinus was 4.4 +/- 2.1 mm and two years later it was 8.2 +/- 3.7 mm. The difference was -1.53 (p = 0.1590). The cutaneous reactivity to D. farinae was 4.6 +/- 2.2 mm in the first evaluation and 8.3 +/- 4.7 mm two years later. The difference was -2.63 (p = 0.0470). CONCLUSIONS: This study showed a significant reduction of specific cutaneous reactivity induced by Dermatophagoides SIT. In the control group the cutaneous reactivity to Dermatophagoides revealed an increment.

Home gardening may be a risk factor for contact dermatitis to Alstroemeria.

BACKGROUND: Occupational allergy among florists and people who work in cut flower production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been previously reported. The allergen involved in sensitization is tulipalin A (alpha-methylene-gamma-butyrolactone). CASE REPORT: We describe the case of a 65-year-old woman who developed severe dermatitis on her right thumb, index and middle fingers and less severe dermatitis on her left palm and front of forearm with occasional itching of the neck and face after taking up home gardening activities, including cutting flowers such as Alstroemeria. METHODS: The patient and three healthy individuals were submitted to epicutaneous tests with the European standard series, the plant series, and stem portions of three suspected ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion. RESULTS: Patch tests performed in our patient, revealed an extreme reaction (+ + +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+ +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an irritant reaction to garlic and negative results to diallyl disulfide and the other components investigated. Patch tests performed in the healthy individuals revealed negative. CONCLUSIONS: We stress the importance of Alstroemeria as a cause of allergic contact dermatitis not only in workers involved in the flower trade, but also in other people that come into contact with this plant in their leisure activities.

Home gardening may be a risk factor for contact dermatitis to Alstroemeria / La jardinería puede ser un factor de riesgo de dermatitis de contacto por alstroemeria

Background: Occupational allergy among florists and people who work in cut flower production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been previously reported. The allergen involved in sensitization is tulipalin A (alpha-methylene-gamma-butyrolactone). Case report: We describe the case of a 65-year-old woman who developed severe dermatitis on her right thumb, index and middle fingers and less severe dermatitis on her left palm and front of forearm with occasional itching of the neck and face after taking up home gardening activities, including cutting flowers such as Alstroemeria. Methods: The patient and three healthy individuals were submitted to epicutaneous tests with the European standard series, the plant series, and stem portions of three suspected ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion. Results: Patch tests performed in our patient, revealed an extreme reaction (+ + +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+ +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an irritant reaction to garlic and negative results to diallyl disulfide and the other components investigated. Patch tests performed in the healthy individuals revealed negative. Conclusions: We stress the importance of Alstroemeria as a cause of allergic contact dermatitis not only in workers involved in the flower trade, but also in other people that come into contact with this plant in their leisure activities

Antecedentes: La alergia ocupacional entre las floristas y en los trabajadores de producción de flores de corte de cultivos de Alstroemeria (lirio Peruano o lirio Inca) fue ya objeto de descripción. La Tulipalina A (alfa-metileno-gama-butirolactona) es lo alergeno involucrado en la sensibilización. Caso clínico: se presenta un caso de una paciente de 65 años que ha iniciado una dermatitis grave en los 1º, 2º y 3º dedos de la mano derecha, bien como una dermatitis de intensidad moderada en la área palmar izquierda y vista anterior de lo antebrazo homolateral. Ocasionalmente, los síntomas se acompañan de prurito de la cara y cuello, en el decurso de actividades de jardinaje en su casa, incluyendo el corte de flores de Alstroemeria. Métodos: Fueron realizadas pruebas epicutáneas con la serie estándar europea, la serie de plantas, y porciones de tallo de tres plantas sospechas (Alstroemeria, Lilium y Zantedeschia), ajo y cebolla. Resultados: Las pruebas revelaron una reacción severa (+++) a Alstroemeria y alfa-metileno-gama-butirolactona, una reacción intensa (++) a propolis y mixtura de alquitranes de la madera, una reacción ligera (+) a bálsamo Perú, una reacción irritativa a ajo y resultados negativos a dialil disulfido, bien como a todos los demás estudiados. Conclusiones: Este caso clínico reporta la importancia de la Alstroemeria como inductor de dermatitis de contacto alérgica, non solo en trabajadores de floricultura, pero también en individuos comunes que puedan contactar con esta planta en sus actividades de tiempos libres