Erythropoietic protoporphyria: case reports for clinical and therapeutic hints.

BACKGROUND: Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity. Herein we report our case series describing the successful use of cimetidine and analyzing potential phenotype-genotype correlations. CASE PRESENTATION: This case series describes five patients presented to our Rheumatology Service complaining sun sensitivity. Blood exams and genetic analysis were consistent with the diagnosis of erythropoietic protoporphyria. Four of 5 patients received cimetidine in addition to standard therapies and the effect of treatment was evaluated by Erythropoietic Protoporphyria - Quality of Life questionnaire. CONCLUSIONS: Erythropoietic protoporphyria usually manifests in early childhood after a short sun exposure. Skin manifestations are the main reason for investigations, although sometimes they can be more subtle, leading to a significant diagnostic delay. Skin diseases in children can have profound effects on their family and social relationships. A treatment with cimetidine appears to be an excellent therapeutic option in children with Erythropoietic protoporphyria.

Celiac Disease Frequency Is Increased in IgE-Mediated Food Allergy and Could Affect Allergy Severity and Resolution.

OBJECTIVES: An increased frequency of celiac disease (CeD) has been reported in severe Immunoglobulin E (IgE) -mediated food allergy (FA). This observation requires confirmation, and whether CeD affects FA severity and resolution is unknown. The study aims to estimate the prevalence of CeD in patients with FA and to investigate whether CeD affects FA severity and oral tolerance. METHODS: Consecutive patients with FA referred for allergen reintroduction, either to evaluate allergy resolution or to start oral immunotherapy (OIT), were evaluated for CeD and for FA severity. The primary outcome was the prevalence of CeD. Secondary outcomes were the frequency of severe FA and the level of clinical tolerance at study entry and at last follow-up in patients with isolated FA versus patients with FA + CeD. RESULTS: Two hundred twenty-eight patients were included. CeD was confirmed in 15 patients (6.6%) of whom, 8 patients had a previously established diagnosis of CeD and were on a gluten-free diet. Severe FA was observed in 12 patients with FA + CeD (80%) versus 88 patients with FA (42%) ( P = 0.006). At baseline, patients with FA + CeD had significantly higher median allergen-specific IgE levels [61.8 kU/L; interquartile range (IQR) 11.6-279.0] compared to patients with FA (20.3 kU/L; IQR 2.9-72.7) ( P < 0.001). Complete clinical tolerance was observed in 1 of 15 patients (7%) with FA + CeD versus 98 of 205 patients (48%) with FA ( P = 0.002). CONCLUSIONS: CeD is highly prevalent in patients with FA and could affect FA severity and response to OIT. CeD screening should be considered in patients with severe or persistent FA.

A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin's physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.

Risk factors for discontinuing oral immunotherapy in children with persistent cow milk allergy.

BACKGROUND: There are no universally accepted criteria for discontinuing milk oral immunotherapy (MOIT) in patients with persistent cow milk allergy (CMA) and little data are available on predictive risk factors for dropping out from oral immunotherapy (OIT), due to allergic reactions or other reasons. METHODS: We retrospectively reviewed clinical records of patients with persistent severe CMA undergoing MOIT in a tertiary care center hospital to investigate risk factors associated with discontinuation of OIT. Persistent and severe allergy was defined as the history of systemic reactions and any milk protein-specific IgE level >85 kU/ml. All patients were first admitted for an in-hospital rush phase eventually followed by an at-home dose increase. We evaluated the effect of various factors on two primary outcomes: the highest dose of milk ingested during the in-hospital rush phase and during the home OIT phase. RESULTS: We identified 391 patients, of whom 131 met the inclusion criteria for the retrospective study, 54 females and 77 males. Data of the home OIT phase were available for 104 patients (27%). Regarding the home OIT outcome, an association for having a cow milk avoiding diet was found with reaching a dose below 10 ml during the in-hospital rush phase (relative risks [RR]: 2.33, confidence interval [CI]: 0.85; 6.42), an age above than 10 years from the time of admission (RR: 3.29, CI: 0.85; 12.73), and a higher total number of reactions occurred during the hospitalization (RR: 1.54, CI: 1.02; 2.32), whereas the presence of respiratory reactions with wheezing (RR: 1.93, CI: 0.49; 7.61) and an IM adrenaline use was related to a higher risk of having an OIT still in progress (RR: 5.47, CI: 0.33; 7.73). CONCLUSIONS: In this cohort of children with persistent CMA undergoing OIT who presented with respiratory reactions with wheezing, the development of anaphylaxis with the need for IM adrenaline, and age above 10 years were predictors of poor long-term outcome.

Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP).

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

Life-threatening anaphylaxis in children with cow's milk allergy during oral immunotherapy and after treatment failure.

BACKGROUND: Oral immunotherapy (OIT) is a promising therapeutic approach for children with persistent IgE-mediated cow's milk allergy (CMA) but data are still limited. OBJECTIVE: To analyze the prevalence of life-threatening anaphylaxis in children with persistent CMA undergoing OIT and to evaluate potential risk factors. METHODS: This is a retrospective cohort study among children with persistent CMA undergoing OIT over a 20-year period, following a specific Oral Tolerance Induction protocol. Adverse reactions during the whole period and data on long-term outcome were registered. Descriptive and nondescriptive statistics were used to describe data. RESULTS: Three hundred forty-two children were evaluated. During OIT, 12 children (3.5%) presented severe anaphylactic reactions that needed an adrenaline injection. None required intubation, intensive care unit (ICU) admission, or showed a fatal outcome. Five of them abandoned OIT, five reached unrestricted diet and the others are still undergoing OIT. As far as outcome is concerned, 51.2% reached an unrestricted diet; 13.5% are at the build-up stage; and 28.0% (97 patients) stopped the OIT. Among these 96 children, 6.3% experienced a severe reaction induced by accidental ingestion of milk with two fatal outcomes. CONCLUSIONS: The risk of life-threatening reactions was nearly two times lower (3.5% vs. 6.3%) among patients assuming milk during OIT than in those who stopped the protocol. A trend in favor of more severe reactions, requiring ICU admission, or fatal, was shown in patients who stopped OIT.

Omalizumab effectiveness in patients with a previously failed oral immunotherapy for severe milk allergy.

BACKGROUND: Some studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt. METHODS: Single-center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8-24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8-week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re-evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL). RESULTS: During OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all. CONCLUSION: In this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

Unilateral leg swelling in a newborn.

A female neonate was born with asymmetric lower limbs, the right leg appearing enlarged, with thickened, reddish-purple skin and ectasic superficial reticulum (figure 1A,B). Limb pulses were present and symmetrical. The girl's family history and prenatal scans were unremarkable. Laboratory findings were within the normal range, except for a mild thrombocytopenia (90 000/µL), which spontaneously resolved during the next few days. A leg X-ray and the Doppler analysis ruled out the presence of calcifications and venous varices, respectively. Ultrasound showed significant skin thickening, with marked dermal hypertrophy and hyperechogenicity. Magnetic resonance showed circumferential thickening of the derma, with mild hypertrophy of some perforating vessels (figure 2). A biopsy of the right thigh showed capillary malformations on histology.

A bullous rash.

A 3-year-old boy presented with a 5-day history of bullous skin lesions localised mainly in the upper and lower limbs and in the genital region (figure 1). Lesions were not pruritic nor painful and showed a central crust. There was no family history of skin disorders or autoimmune diseases. The child never had fever and his physical examination was otherwise unremarkable.

Pyogenic granuloma arising within capillary malformations in children: A case report and literature review.

Pyogenic granuloma (PG) is an acquired benign vascular hyperplasia. Even though PG is not so rare, its etiology is still unclear. Assuredly, an association between vascular anomalies and PG is an extremely rare finding, and a proper management of these cases is not well standardized to date. Herein, we report our experience with a giant PG arising spontaneously within a port-wine stain of the thorax. Previous cases reported in the pediatric literature and strategies of treatment are also discussed.

Early introduction oral immunotherapy for IgE-mediated cow's milk allergy: A follow-up study confirms this approach as safe and appealing to parents.

INTRODUCTION: Early introduction oral immunotherapy (E-OIT) in the first year of life can be a safe treatment for infants with cow's milk allergy (CMA). Once the protocol is completed, doubts remain whether children achieve tolerance or remain desensitized. According to current guidelines, this is determined by an avoidance period followed by a re-exposure to the food allergen during an in-hospital oral food challenge (OFC). In real life, this approach can be complicated, time-consuming, and anxiety-provoking for parents. We assessed the long-term safety of E-OIT for CMA in a cohort of children who switched to an unrestricted diet without testing the achievement of tolerance at the end of the OIT protocol. MATERIALS AND METHODS: We performed a descriptive analysis of the clinical follow-up of a cohort of children diagnosed with IgE-mediated CMA and undergoing E-OIT protocol in their first year of life. In a previous publication, the same cohort of patients had been studied to assess the feasibility of E-OIT for CMA. In the present study, we reported the results of a telephone survey, carried out through a questionnaire to their families enquiring about milk consumption and other ongoing atopic conditions of children. RESULTS: After an average of 4 years from the start of E-OIT, 62/73 patients (85% of the historical cohort) participated in the survey. Among them, all 56 patients who had previously successfully completed the protocol reported an unrestricted cow's milk intake. Ninety-three percent of these children did not experience any further allergic reactions, while the remaining 7% described only mild and transitory reactions until the 6-month period after the end of the protocol. CONCLUSIONS: This study confirmed the long-term safety of E-OIT for CMA and challenged the paradigm of the need for allergen food withdrawal to discern between desensitization and tolerance. It could be a starting point for planning future trials on this issue.

Young child with painful edema and purpura: a case report.

BACKGROUND: We reported the case of a two-old-year boy with a painful acute hemorrhagic edema. This is a self-limited benign condition: usually, affected children are well appearing and this strongly support the diagnosis. In the opposite, in our case, we observed a painful presentation of the edema. Therefore, we demonstrated that rarely, this condition could have also a painful presentation. CONCLUSIONS: This case report helps clinician to know that also acute hemorrhagic edema could have a painful presentation, so we must considered it in the differential diagnosis with sepsis, sickle cell crisis and child abuse. We believe that these findings will be of interest to pediatricians.