Severe Protein Loss in a 6-month-old Exclusively Breastfed Infant with Atopic Dermatitis.

Protein loss is often the result of kidney or intestinal disease (protein-losing enteropathy) and can cause a number of serious, potentially life-threatening complications such as hypotension, thrombocytosis, electrolyte imbalance, and cerebellar ischemia. Recent research suggests an association between extremely severe atopic dermatitis (AD) and allergic enteropathy. An exclusively breastfed 6-month-old infant was admitted to our institution due to failure to thrive, electrolyte imbalance, and severe AD (SCORing Atopic Dermatitis; SCORAD 40). On admission, the infant was in poor general condition, dehydrated, malnourished (bodyweight 4870 g, -3.98 z-score), with exudative erythematous morphs scattered throughout the body. Initial laboratory results showed microcytic hypochromic anemia, hypoalbuminemia, hypogammaglobinemia, thrombocytosis, hyponatremia, high values of total immunoglobulin E (IgE), and eosinophilia. Polysensitization to a number of nutritional and inhalation allergens was demonstrated, and an exclusive amino acid-based formula has been introduced into the diet. During the hospital course, the patient developed superficial thrombophlebitis and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Eosinophilia was found in a small intestine biopsy sample. Due to severe hypogammaglobulinemia, skin infections, and bacteremia, the differential diagnosis included primary immune deficiency (STAT3 deficiency, DOCK8 deficiency, PGM3 deficiency, IPEX), but all available immunological tests were unremarkable. Exclusive amino acid-based formula diet was continued in the infant, with topical corticosteroids under wet-dressing therapy and intravenous immunoglobulin replacement therapy. With the gradual improvement of the general condition, the introduction of solid foods was started according to the findings of allergy testing. At 17 months of age, the patient gained weight and his skin status has been improving, although frequent use of topical corticosteroids was necessary. There were no infections, no anemia or thrombocytosis, and albumin and immunoglobulin supplementation were no longer required. The main mechanism of protein loss in infants with extremely severe atopic dermatitis is probably due to damaged skin, and partially due to the eosinophilic inflammation of the small intestine. Immunoglobulin loss, potentiated by physiological or transient hypogammaglobulinemia in infants, poses a very high risk for severe, potentially life-threatening infections.

Comparison of the effectiveness of two combinations of antibiotic used for perioperative prophylactic therapy during radical cystectomy: A retrospective cohort study.

INTRODUCTION: This retrospective cohort study aimed to compare primary and secondary outcomes of patients undergoing radical cystectomy according to two different perioperative antimicrobial therapy protocols in 2016. METHODS: In this single-center, retrospective cohort study, we investigated data of 104 patients undergoing radical cystectomy due to bladder cancer from January 1, 2016, to December 31, 2016. According to perioperative antimicrobial prophylaxis, patients were divided into two groups: 48 patients received piperacillin/tazobactam 3x4.5 g intravenously (IV) combined with metronidazole 3x500 mg IV, and 56 patients received ceftriaxone 1x2 g IV combined with metronidazole 3x500 mg IV. All patients received the first dose of antibiotics 24 hours prior to the operative procedure, and it continued over the next 48 hours after the procedure. We analyzed and compared data from various primary and secondary outcomes for both groups of patients. RESULTS: In the group of patients receiving the combination of the piperacillin/tazobactam with metronidazole, the length of postoperative hospitalization was shorter (14 vs. 16 days, Z=2.24957 p=0.02383), leukocyte blood count on the first postoperative day was lower (9.80 vs. 11.15, p=0.01384), and hospital-acquired pneumonia was less common (2.08% vs. 12.5%, p=0.04688) than in the group receiving a combination of ceftriaxone and metronidazole. CONCLUSIONS: In radical cystectomy, perioperative antimicrobial prophylaxis protocol using piperacillin/tazobactam combined with metronidazole proved to be more effective than the combination of ceftriaxone with metronidazole.

The Role of Combined Multichannel Intraluminal Impedance-pH Monitoring in Infants with Brief, Resolved, Unexplained Events.

PURPOSE: Data on the relationship between gastroesophageal reflux (GER) and brief resolved unexplained events (BRUE) in infants is scarce. The aim of this study was to identify the characteristics of combined multichannel intraluminal impedance-pH (MII-pH) monitoring in infants who have experienced BRUE. METHODS: We conducted a prospective study of infants who were hospitalized on account of BRUE and required 24-hour MII-pH monitoring. RESULTS: Twenty-one infants (mean age, 4.7 months; range, 0.9-8.9 months; male/female, 11/10) participated in this study. BRUE symptoms associated with GER were found in 10 infants (47.6%). Based on the RI on pH-metry alone, only 7 (33.3%) infants were diagnosed with GERD. More than 100 GER episodes detected by MII were found in 10 (47.6%) infants. Nineteen percent of infants were diagnosed with GERD based on both pH and MII. CONCLUSION: Both acid and non-acid reflux seem to play a significant role in the pathogenesis of GER-related BRUE in infants.

Fecal Calprotectin as a Biomarker of Food Allergy and Disease Severity in Children with Atopic Dermatitis without Gastrointestinal Symptoms.

Fecal calprotectin (FCP) is a biomarker of intestinal inflammation and has recently been proposed as a diagnostic biomarker of food allergy (FA) in children. The aim of this study was to compare FCP level in infants and children under 4 years old with 1) atopic dermatitis (AD) with food allergy (FA) and 2) children with AD and without FA with the results in healthy controls. In total, 46 infants and children (mean age 14 months ± 12) diagnosed with AD were divided into two groups: G1, children with atopic AD with FA (n=28) and G2, children with AD without FA (n=18). The control group (G3) was made up of healthy children of the same age (n=18). The median FCP was significantly higher in G1 compared with G2 (G1: median 154, IQR 416 µg/g vs G2: median 41.3, IQR 59 µg/g; P=0.0096). The median FCP in children with AD and FA was significantly higher before elimination diet in comparison with FCP after 3 months of elimination diet (median 154, IQR 416 µg/g vs median 35, IQR 23 µg/g; P=0.0039). The level of FCP was significantly positively correlated with the SCORAD score (r=0.5544, P=0.0022). Our study showed a significant difference in level of FCP in patients with AD without FA compared with patients with AD and FA. We also found a positive correlation of FCP with SCORAD score, a biomarker of AD severity. New studies are needed to investigate the role of FCP as a biomarker of FA in children with AD.

Darier Disease Presenting with Recurrent Kaposi Varicelliform Eruption in a 10-year-old Boy with Seborrheic Dermatitis.

We present a case of a 10-year-old boy with a longstanding history of seborrheic dermatitis (SD) referred to the Allergy and Immunology Department for recurrent Kaposi varicelliform eruption (KVE) secondary to herpes simplex 1 (HSV-1) infection and possible primary immunodeficiency. The patient was the second child of non-consanguineous parents, with an older, healthy brother. Family history was negative for primary immunodeficiency and skin disorders. The patient's skin problems began in infancy when he was diagnosed and treated by a dermatologist for SD. From preschool age, he was under the care of a pediatric neurologist and a defectologist for a sensory processing disorder. For the last two years, the patient had been receiving chlorpromazine therapy for aggressive behavior. The first episode of KVE was diagnosed at the age of six, following potent topical corticosteroid therapy for SD and sun exposure, another known risk factor for HSV infection. After the third KVE episode, prophylaxis with oral acyclovir was initiated. The skin changes were treated with topical steroids and oral antibiotics during disease flares, with poor clinical response. On presentation, the patient was in good general health, adipose, and of unremarkable somatic status, except for numerous symmetrical yellowish-brown keratotic papules and plaques on the forehead, cheeks, and the lateral side of the neck (Figure 1). The nail plate had multiple red and white longitudinal streaks and V-shaped notches on the distal free end of the nail plate (Figure 2). The allergy tests revealed increased total immunoglobulin E (IgE) and sensitization to ragweed. Immunological workup showed normal immunoglobulins and good specific immunity (good vaccine response and normal humoral response to HSV-1) but a decreased number of T- cells (CD3+ 1020/µL (1320-3300), CD3+CD8+ 281/µL (390-1100) with normal T-cell response after antigen stimulation. The diagnosis of Darier disease (DD) was confirmed based on medical history, clinical findings and histological finding of focal suprabasal acantholysis and dyskeratosis (Figure 3). Low-dose oral retinoid therapy was initiated with modest clinical response after 6 months of therapy. In the light of recent publication (1), we initiated intravenous immunoglobulin (IVIG) substitution (400 mg/kg every month) with excellent clinical response. After 4 months, the patient's skin improved in terms of reduced inflammation, scab healing, and reduced itching. Acyclovir prophylaxis was continued. The patient had no new episodes of KVE during follow-up. Kaposi's varicelliform eruption (KVE) or eczema herpeticum occurs in a chronic inflammatory skin disease such as atopic dermatitis (AD), SD, Hailey-Hailey disease, allergic contact dermatitis, psoriasis, and DD (2). It is considered a dermatologic emergency due to its high mortality rate if misdiagnosed or left untreated (3). DD is a rare autosomal dominant genodermatosis of variable expressivity caused by mutations in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase (SERCA2) highly expressed in keratinocytes (4). The onset of the disease usually occurs between the ages of 6 and 20 years. There are several clinical variants of DD: hypertrophic, verrucous, vesicular-bullous (dyshidrotic), erosive, and predominantly intertriginous forms (4). The fact that skin lesions occurred in infancy and a negative family history for skin diseases could be the reason our patient was initially misdiagnosed with seborrheic dermatitis. Due to the variable expressivity of the disease, it is impossible to exclude the diagnosis in other family members, and genetic testing of the patient and family members is therefore planned. A co-occurrence of neuropsychiatric abnormalities such as epilepsy, mental impairment, and mood disorders have been reported in patients with Darier disease, and these disorders were also present in our patient (5), indicating a correct diagnosis. Patients with DD have a high propensity for severe viral, bacterial, and fungal skin infection, probably due to local disruption of the skin barrier function or as the result of an underlying defect in general host defence (6). The occurrence of KVE in patients with DD is rare (7) and possibly caused by a disturbances in cell-mediated immunity (8). Despite abnormal findings in cellular immunity in some patients with DD, no consistent or specific abnormalities of the immune system have yet been demonstrated (6). Our patient had a decreased number of cytotoxic T-cells with normal T-cell response after antigen stimulation (in contrast with the findings of Jegasothy et al. (6)) and normal humoral response to HSV-1 infection. Recurrent KVE in our patient could be related to immune system dysfunction as an additional risk factor, along with impaired skin barrier. The excellent clinical response to IVIG speaks in favor of the role of antibody immune response in preserving the skin barrier. Occurrence of KVE in patients with mild DD (as in the case of our patient) and in some patients immediately preceding clinical skin manifestations of disease, argues very strongly against the second supposition. The severity of DD is variable and has a chronic course with frequent exacerbations and remissions. Known exacerbating triggers are: heat, sweat, sun exposure, friction, medication, and infection (9,10). The disease is chronic, and management is focused on the improvement of the skin appearance, relief of symptoms (e.g., irritation, pruritus, and malodor), and prevention or treatment of secondary infections. Topical (emollients, corticosteroids, retinoids, 5-fluorouracil, tacrolimus, pimecrolimus), physical (excision, electrodessication, dermabrasion, ablative laser, photodynamic therapy), and systemic (oral antibiotics, antiviral drugs, antimicrobial prophylaxis, vitamin A, retinoids) therapies are among the treatment options, all of which are of limited effect (2,11,12). IVIG substitution could be beneficial in some patients with Darier disease (1). In conclusion, this case highlights the association of DD with impaired cellular immunity and indicates the importance of proper diagnosis due to adequate management and avoidance of possible fatal outcomes. However, whether a subtle abnormality of T-cells in DD predisposes the patient to KVE remains unclear. Possible underlying mechanisms should be investigated further.

Alternative Splicing Rescues Loss of Common Gamma Chain Function and Results in IL-21R-like Deficiency.

Inborn errors in interleukin 2 receptor, gamma (IL2RG) perturb signaling of the common gamma chain family cytokines and cause severe combined immunodeficiency (SCID). Here, we report two brothers suffering from chronic cryptosporidiosis, severe diarrhea, and cholangitis. Pan T, B, and NK cell numbers were normal, but immunophenotyping revealed defective B cell differentiation. Using whole exome sequencing, we identified a base pair deletion in the first exon of IL2RG predicted to cause a frameshift and premature stop. However, flow cytometry revealed normal surface expression of the IL-2Rγ chain. While IL-2, IL-7, and IL-15 signaling showed only mild defects of STAT5 phosphorylation in response to the respective cytokines, IL-4- and IL-21-induced phosphorylation of STAT3 and STAT6 was markedly reduced. Examination of RNA isoforms detected alternative splicing downstream of IL2RG exon 1 in both patients resulting in resolution of the predicted frameshift and 16 mutated amino acids. In silico modeling suggested that the IL-2Rγ mutation reduces the stabilization of IL-4 and IL-21 cytokine binding by affecting the N-terminal domain of the IL-2Rγ. Thus, our study shows that IL2RG deficiency can be associated with differential signaling defects. Confounding effects of alternative splicing may partially rescue genetic defects and should be considered in patients with inborn errors of immunity.

Metal allergy as a late-onset complication of the Nuss procedure in a pediatric patient.

We report the case of a 14-year-old boy with pectus excavatum who developed a metal allergy to stainless steel bar as a late-onset complication after the Nuss procedure. He did not have atopic diathesis. Treatment with oral steroids was effective and the metal bar was successfully removed 2 years later.

Successful Treatment of Autoimmune Pulmonary Alveolar Proteinosis in a Pediatric Patient.

BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the intra-alveolar accumulation of surfactant-derived material, which impairs gas exchange and results in respiratory insufficiency. Two major subtypes of PAP are autoimmune and non-autoimmune PAP. The diagnosis relies on clinical presentation, ground glass opacities on CT scan, bronchoscopy with PAS stain of BAL fluid (BALF), lung biopsy with PAS-positive material in the alveoli, and the presence of anti GM-CSF antibodies in serum or BALF for an autoimmune subtype. The therapeutic approach to pediatric cases varies according to age and the general clinical state of the child; however, whole lung lavage (WLL) and inhaled or subcutaneous GM-CSF are generally first-line therapy. CASE REPORT We report a unique case of an autoimmune type of PAP in a 12-year-old boy, who underwent successful bilateral lung transplantation after inefficacious treatment with GM-CSF, and who developed post-transplant lymphoproliferative disease (PTLD) and was successfully treated with a chemotherapeutic protocol. CONCLUSIONS Although lung transplantation is a rarely used therapeutic approach for patients with an autoimmune subtype of PAP, in cases of inefficacious treatment with other modalities, lung transplantation should be considered.

Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report.

BACKGROUND: Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. CASE REPORT: We report the case of an 8-year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein--AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). CONCLUSIONS: The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis.

Urates in exhaled breath condensate as a biomarker of control in childhood asthma.

OBJECTIVE: The aim of this study was to (1) investigate the possibility to use urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation and control in childhood asthma and (2) explore their association with other biomarkers of airway inflammation and clinical indices of asthma control (Asthma Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use, time from last exacerbation [TLE]. METHODS: This cross-sectional study comprised 103 consecutive patients (age 6-18 years) divided in groups of uncontrolled ([NC], n = 53) and controlled asthma ([C], n = 50). Measured lung function and biomarkers included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), exhaled NO (FENO), pH and urates in EBC and exhaled breath temperature (EBT). RESULTS: Statistically significant differences were found between groups for EBC urates, EBC pH and EBT (NC versus C: EBC urates, median [IQR], µmol/L; 10 [6] versus 45 [29], p < 0.001; EBC pH, mean [SD], 7.2 [0.17] versus 7.33 [0.16], p = 0.002; EBT mean [SD], °C; 34.26 [0.83], versus 33.90 [0.60], p = 0.014). EBC urates showed significant association with TLE and FENO (r = 0.518, p < 0.001; r = 0.369, p = 0.007, respectively) in NC, and EBC pH (r = 0.351, p < 0.001), FEV1 (r = 0.222, p = 0.024), ACT (r = 0.654, p < 0.001), PAQLQ (r = 0.686, p < 0.001) and prn salbutamol use (r = -0.527, p < 0.001) in all asthmatics. CONCLUSION: In our study, EBC urates were found to be the best single predictor of asthma control and underlying airway inflammation. Our results provide evidence supporting the potential utility to use EBC urates as an additional non-invasive biomarker of control in childhood asthma.

Pulmonary arteriovenous malformations presenting as difficult-to-control asthma: a case report.

INTRODUCTION: Although pulmonary arteriovenous malformations are relatively rare disorders, they are an important part of the differential diagnosis of common pulmonary problems, such as hypoxemia, dyspnea on exertion and pulmonary nodules. CASE PRESENTATION: An 11-year-old Croatian boy of Mediterranean origin with a history of asthma since childhood was admitted to our hospital for evaluation of difficult-to-control asthma during the previous six months. A chest X-ray showed a homogeneous soft tissue mass in the lingual area. Computed tomography angiography of the thorax showed two pulmonary arteriovenous malformations, one on each side of the lungs. Diagnosis of hereditary hemorrhagic telangiectasia was made clinically by Curaçao criteria. Genetic analysis revealed a mutation in the endoglin gene. The patient was treated with embolotherapy with good clinical outcome. CONCLUSION: We present a case of pulmonary arteriovenous malformations masquerading as refractory asthma.

Exercise-induced anaphylaxis after ingestion of sandwich with soy containing canned tuna: case report.

We report a case of a 17-year-old female adolescent who experienced an episode of exercise-induced anaphylactic reaction following ingestion of tuna sandwich (from soy containing canned tuna). Her medical history revealed that she had previously had one episode of urticaria after ingestion of sulfamethoxazole with trimethoprim and anaphylactic reaction after ingestion of sunflower nuts. Skin prick tests and specific immunoglobulin E antibody to tuna were negative, and to soy were positive. Treadmill exercise induced test in fasting state and 1 hour after a fresh tuna meal and meal not containing soy were negative. However, an exercise challenge test one hour after soy ingestion resulted in pruritus of hands, shoulders and back, urticarial lesions of the face and neck with angioedema of the lips and eyelids, hoarseness, tachycardia and anxiety.