Vasculitis-like Palpable Purpuric Rash Induced by Decapeptyl in a Pediatric Patient Diagnosed Central Precocious Puberty

Central precocious puberty (CPP) is defined as the appearance of secondary sexual signs in girls younger than eight years of age or the onset of menarche before the age of 10 years. Gonadotropin-releasing hormone analogs (GnRHa) are the most effective therapy in CPP. Drug-induced hypersensitivity vasculitis is an inflammation of blood vessels, which may be due to the use of a number of pharmacologic agents. This case report describes drug-induced vasculitis in a girl being treated with Decapeptyl. A 7.25 year-old girl was admitted to Pediatric Endocrinology outpatients with premature breast development. She was diagnosed with CPP on the basis of physical examination and laboratory findings and tripoteline acetate (Decapeptyl®) treatment was initiated. She experienced multiple widespread skin rashes and mild abdominal pain with high temperature eight hours after the second dose of Decapeptyl. She was admitted to hospital with the diagnosis of drug-induced vasculitis and a single dose of intravenous methyl-prednisolone (1 mg/kg) and oral cetirizine was given. Her blood and urine analysis revealed no other organ involvement, other than skin. On the third day, the purpuric lesions began to resolve and had completely disappeared by the sixth day. Her treatment for CPP was switched to Depot Leuprolide acetate and she continued her treatment for two years uneventfully. To the best of our knowledge, this is the first report of a child with CPP experiencing drug-induced vasculitis due to tripotelin injection. Effective treatment may be continued by switching to an alternative gonadotropin releasing hormone analog.

Cutaneous Allergic reactions to pine processionary caterpillar (Thaumetopoea Pityocampa): a complicated cutaneous reaction in an infant and review of the literature.

BACKGROUND: Thaumetopoea Pityocampa (TP) are frequent in the Mediterranean region especially affecting forest workers in pinewood areas. The common symptoms include swelling, rash or burns like any form of dermatitis. The reactions can be triggered by mechanical, chemical or allergic factors and the `allergic` reaction is caused by sensitization to a hair protein named `thaumetopoein`. This protein triggers the IgE mediated reaction resulting in the mast cell degranulation causing urticaria. Different kinds of allergic reactions like urticaria or anaphylaxis have been reported previously commonly in adults, especially in forest workers while severe reactions without direct contact are rare in pediatric population. CASE: A 28 month old healthy boy was admitted to Near East University Pediatric Allergy and Immunology Outpatient Clinic in March with complaints of pain, hyperemia and swelling on the left hand. His complaints had started the day before his admission just after walking around in their garden which is surrounded by pine trees. On admission, his physical examination revealed serious edema and hyperemia on his left hand limiting his finger movements with a few bullae on the skin. His temperature was 38 C and the other vital parameters were normal. Based on hyperemia, swelling and high acute phase reactants he was hospitalized with the differential diagnosis of soft tissue inflammation and cellulitis. The case was treated with iv antihistamines, systemic steroids and antibiotics. CONCLUSIONS: Pine processionary (PP) is an important irritant and allergen especially in endemic areas like Cyprus which is a Mediterranean Country. It must be kept in mind in case of local or generalized urticaria, dermatitis, bullae and other allergic reactions even if there had been no direct contact with PP. Systemic involvement with fever and elevated acute phase reactants in infancy may necessitate hospitalization and intravenous treatment. Hereby, we reported an infant who presented with fever in addition to severe cutaneous lesions following the exposure to TP without direct contact. This is the first case reported from North Cyprus.

Characteristics of allergic proctocolitis in early infancy; accuracy of diagnostic tools and factors related to tolerance development.

OBJECTIVE: We aimed to overview clinical characteristics of FPIAP with the results of diagnostic tools like APT, SPT and fecal calprotectin levels and the factors associated with tolerance development. METHODS: All patients diagnosed FPIAP at the outpatient clinic between January 2015 and January 2019 were enrolled retrospectively. Data about clinical characteristics, APT or SPT results, fecal calprotectin levels, suspected triggering foods, diet and tolerance status were obtained from the hospital database program and analyzed. RESULTS: 169 infants with F/M ratio 78/91 were enrolled. The mean age of the study population was 3.68 months (1-35 months, mean age 3.68 ± 4.33). APT was performed 137 of the participants and 126 (92%) of them were positive to at least one food allergens, 14 (48.2%) patients had positivity to at least one of the food allergens on SPT. Specific IgE were done in 90 patients and 12 (13.3%) revealed positive results. Two groups of patients developing tolerance before and after 18 months of age were evaluated; mucoid diarrhea, family history allergic diseases, cow's milk sensitivity and multiple allergen triggers were statistically significant risk factors for delayed tolerance according to univariate logistic analysis. However, none of these factors were revealed statistical significance in multivariate logistic analysis. CONCLUSIONS: Our study revealed that APT may be a useful tool for programming the elimination diet in breastfeeding mothers. SPT, specific IgE and fecal calprotectin are not necessary for FPIAP management. Multivariate regression analysis showed that none of the evaluated parameters had statistically significant relationship with the tolerance development.

Steroid sparing effect of sublingual immunotherapy: real life study in mono/polisensitized children with asthma.

AIM: Steroid-sparing effect of sublingual immunotherapy (SLIT) in mono/polisensitized asthmatic children were evaluated. MATERIALS AND METHODS: Children undergoing allergen-specific SLIT between 2010 and 2014 were included. Asthma control and usage/dose of inhaled corticosteroid (ICS) in the previous year was determined. Asthma control without ICS need ≥6 months was defined as 'ICS avoidance'. RESULTS: 90 children (mean ± SD age 8.92 ± 4.17 years) were enrolled, 56.7% (n = 60) being polysensitized. Mono, 2-simultaneous and multiple-pollen-mix allergen SLIT were prescribed in 84.4, 17.8 and 7.8%, respectively. ICS was avoided in 70%, with no significant difference in mono- versus poly-sensitized patients. ICS-avoidance rates in mono-allergen, pollen-mixture and 2-simultaneous-allergen SLIT were 93.6, 83.3 and 73.7%, respectively. Longer-duration SLIT resulted in significantly more ICS-avoidance (p:0.0001). CONCLUSION: SLIT with mono/multiple-mixed/simultaneous allergens in childhood asthma resulted in retained-avoidance of ICS. Steroid-sparing effect of SLIT in polysensitized children warrants further investigation.

Prevalence of Mediterranean FeVer Gene Mutations in Turkish Cypriot Population.

OBJECTIVES: This study aims to determine the carrier frequency and the most common mutations of the Mediterranean FeVer (MEFV) gene in healthy Cypriot population of Turkish origin. PATIENTS AND METHODS: A total of 296 healthy participants (102 males, 194 females; median age 30 years; range 1 to 81 years) were evaluated. The exon 2, 3, 5 and 10 of MEFV genes were amplified by polymerase chain reaction. RESULTS: The participants demonstrated an extremely high carrier rate (12.5%). Most commonly detected mutations were E148Q and A74S, with rates of 7.3% and 2.8%, respectively. CONCLUSION: Mediterranean FeVer gene mutation types and carrier rates in Turkish Cypriot population are different than other Mediterranean populations in the region. MEFV mutation carriage is frequent in North Cyprus and familial Mediterranean fever might be one of the causes for end stage renal disease in Turkish Cypriots.

Prevalence of Thalassemia Trait & Iron Deficiency Anemia during Infancy in 2011-2013 in a Thalassemia Prevalent Region: North Cyprus.

BACKGROUND: Iron Deficiency Anemia (IDA) is an important health problem all around the world especially in developing countries. In the Mediterranean countries another prevelant reason of anemia is Thalassemia. Certain strategies had been established as a government policy to reduce prevalence in North Cyprus, such as pre-marital screening of Thalassemia. The prevalence of thalassemia trait has not been evaluated since then. The aim of this study was to detect the prevalence of IDA, thalassemia trait in infants under regular follow-up and to evaluate the compliance to prophylactic iron supplementation (PIS) and its effect on IDA. METHODS: Healthy children admitted to Department of Pediatrics, Near East University Hospital, in 2011-2013 were included. Data of anthropometric measurements, parental thalassemia trait status, duration of PIS usage, complete blood count, ferritin levels and hemoglobin electrophoresis were collected from hospital database program. Anemic children were grouped as IDA, thalassemia trait, both IDA and thalassemia trait and others. RESULTS: Eighty-nine infants with a mean age 13.52±2.09 mo were included. Compliance with PIS recommendation was 85.3% and, the mean duration of iron usage was 6.44±3.18 mo. IDA and thalassemia trait were found to be 11.2% and 4.5% respectively, while 3.4% of the infants had both IDA and thalassemia trait. CONCLUSION: Prevalence of thalassemia trait was 7.9% demonstrating approximately a 50% decline within 5 decades. This result confirms the success of premarital screening policy in North Cyprus. In addition, prevalence of IDA was relatively low being 14.6% supporting the beneficial effect of PIS on prevention of IDA.

Rare adverse events due to house dust mite sublingual immunotherapy in pediatric practice: two case reports.

Sublingual route, a noninjective way of allergen administration appears to be associated with a lower incidence of severe systemic reactions compared with the subcutaneous route. Local adverse reactions are reported which resolve spontaneously within a few days without need for discontinuation of treatment. Hereby, we report two pediatric cases, one with persistent asthma and the other one with persistent allergic rhinitis. Both were treated by house dust mite sublingual immunotherapy, one of whom developed severe wheezing (grade 2 systemic reaction based on World Allergy Organization subcutaneous systemic reaction grading system) and the other intractable vomiting (grade 3 local reaction based on World Allergy Organization sublingual immunotherapy local adverse events grading system) at the end of the build-up phase which repeated on re-administration of the same dose. Both of those two cases completed their 3-year immunotherapy successfully by patient-based adjustment of the highest tolerated dose of the maintenance.

A milestone in house dust-mite-allergen immunotherapy: the new sublingual tablet S-524101 (actair).

Subcutaneous allergen-specific immunotherapy has long been used in the treatment of allergic rhinitis and/or asthma and its efficacy has been confirmed. However, due to the discomfort of injections and the risk of severe adverse reactions, alternative routes of allergen administration have emerged. Delivery of allergens through the mucosal route had been proposed and investigated thoroughly, confirming the sublingual route to be the most efficacious. Later, the efficacy and safety of this route have been documented by numerous controlled trials both for house dust mite (HDM) and pollens. Recently, sublingual orodispersable grass pollen allergen tablets were in use followed by the newly developed HDM allergen tablets with satisfactory clinical results: Moreover, very recently 1 year of HDM tablet treatment was demonstrated to exert its clinical efficacy 1 year after discontinuation of tablet IT. The persistence of efficacy after only 1 year of treatment is a new and promising era. Currently, Sublingual Immunotherapy is the most easily administered and safe treatment option until more immunogenic, less allergenic and more efficient allergen extracts are developed.

Leptin, ghrelin and calprotectin: inflammatory markers in childhood asthma?

BACKGROUND: Appetite-modulating hormones ghrelin and leptin might be relevant to asthma with their pro-inflammatory effects, and calprotectin has been recognized as a promising marker of inflammation. The purpose of this study was to explore whether asthma, atopy and lung functions has a relation with serum levels of leptin, ghrelin and calprotectin as inflammatory markers in children. METHODS: A cross-sectional study was performed by searching the doctor diagnosed asthma through questionnaires filled in by parents who were phoned, and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to perform skin prick test and spirometry. Participants were divided into Group 1, children with previous diagnosis of asthma, and Group 2, children without previous diagnosis of asthma. RESULTS: One thousand and two hundred questionnaires were distributed and 589 of them were returned filled in. Out of 74 children whose parents accepted to participate in the study, 23 were in Group 1 and 51 were in Group 2. There was no statistical difference in serum levels of leptin, ghrelin, calprotectin, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) , forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) values , and skin prick test results between the two groups (p values are 0.39, 0.72, 0.5, 0.17, 0.5, 0.27, 0.18, and 0.81 respectively). CONCLUSION: In this study the inflammation in asthmatic children could not be shown by using serum leptin, ghrelin and calprotectin levels and this is possibly due to the low number of children with ever asthma and equal skin prick test positivity in both groups. This study is the first study aimed to show the relation between serum calprotectin levels and inflammation in asthma. As this study was a cross-sectional study, further prospectively designed randomized controlled studies are necessary to show the association of these markers and inflammation in asthma.

Rosai-Dorfman disease presenting as mediastinal lymphadenopathy: case report and review of the literature.

A 6-year-old boy presented with recurrent pneumonia and diarrhoea for 3 years. He had extensive mediastinal lymphadenopathy and atelectasis with low serum levels of IgA, IgG and IgG3. An inguinal lymph node biopsy demonstrated histological and histochemical features of Rosai-Dorfman disease. There was emperipolesis and histiocytes were immune-positive for S100 proteins. He responded to corticosteroids and regular infusions of immunoglobulins.

Multiallergen-specific immunotherapy in polysensitized patients: where are we?

Allergen-specific immunotherapy administered by the subcutaneous route was introduced a century ago and has been shown to be effective in the management of allergic rhinitis and asthma. More recently, the sublingual administration of allergen extracts has become popular, especially in European countries, and has also demonstrated efficacy in respiratory allergic diseases. Both modes of allergen administration during immunotherapy have been shown not only to reduce symptoms and the need for medication, but also to prevent the development of additional sensitivities in monosensitized patients, as well as asthma development in patients with allergic rhinitis, with a long-lasting effect after the completion of several years of treatment. Almost all of the well-designed and double-blinded, placebo-controlled studies evaluated treatment with single-allergen extracts. Therefore, most meta-analyses published to date evaluated immunotherapy with single allergen or extracts containing several cross-reactive allergens. As a result, in general, multiallergen immunotherapy in polysensitized patients (mixture of noncross-reactive allergens) is not recommended owing to lack of evidence. Although some guidelines have recommended against the use of multiallergen mixtures, allergists commonly use mixtures to which the patient is sensitive with the rationale that effective immunotherapy should include all major sensitivities. Literature on this subject is scarce in spite of the widespread use worldwide. Here, this issue will be extensively discussed based on currently available literature and future perspectives will also be explored.

Comparing subcutaneous and sublingual immunotherapy: what do we know?

PURPOSE OF REVIEW: Although allergen-specific sublingual (SLIT) and subcutaneous immunotherapy (SCIT) have been demonstrated to be clinically effective with similar immunological responses, head-to-head studies comparing those two modes of allergen administration in terms of onset of clinical improvement along with simultaneous immunological responses and underlying mechanisms of preventive effect are scarce. The present review will update current data on this issue. RECENT FINDINGS: Compared with SLIT, SCIT provides a rapid onset of clinical improvement by eliciting a simultaneous surge in production of T helper 1 (Th1) and T regulatory cell (Treg) cytokines and blocking antibodies. Similar immunological and clinical responses are evoked quite later, with no effect on Immunoglobulin G (IgG)4 levels during SLIT. Increases in TGFß secretion due to nonrelevant allergens during SLIT may explain the preventive effect on new sensitizations. SUMMARY: SLIT and SCIT are both clinically effective in the treatment of respiratory allergic diseases with slight differences in the early phase in terms of onset of clinical efficacy and simultaneous immunological responses. Both SLIT and SCIT induce similar T-cell responses in time, but specific IgG4-blocking antibody responses are more prevalent following SCIT. Further head-to-head studies addressing the preventive effect of monotherapy and the efficacy and immunological responses of nonrelated multiallergen immunotherapy in polysensitized patients are warranted.

Is calprotectin a marker of tobacco smoke related inflammation?: a pilot study in children.

CONTEXT: Environmental tobacco smoke (ETS) related inflammation has an anorexigenic effect through affecting the release of appetite-modulating mediators, leptin and ghrelin. Elevated serum calprotectin levels are found in a variety of inflammatory conditions. OBJECTIVE: To study the relation between ETS and body mass index (BMI), as well as serum levels of leptin, ghrelin and calprotectin. MATERIALS AND METHODS: A cross-sectional study was performed by searching the smoking status of parents. After filling in the questionnaires, parents were phoned and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to calculate their BMIs. Participant children were divided into Group 1 (n = 51), those who are not exposed to and Group 2 (n = 46), exposed to indoor ETS. RESULTS: There were no statistical difference in BMI, leptin and ghrelin levels between Group 1 and Group 2 (p values are 0.85, 0.87 and 0.42, respectively), but serum calprotectin levels were statistically higher in Group 2 (p = 0.003). DISCUSSION AND CONCLUSION: In this study serum levels of calprotectin were found to be higher in children with indoor ETS exposure where no relation was detected with BMI and serum levels of leptin and ghrelin. Increased serum levels of calprotectin might be an indicator of inflammation related to ETS exposure.

Acremonium spp. peritonitis in an infant.

Fungal peritonitis is a rare but serious complication in children on peritoneal dialysis. Clinical presentation of fungal peritonitis is similar to bacterial peritonitis and Candida spp. are the most common agent. Fungal peritonitis has been usually associated with high morbidity, mortality and its treatment is difficult. In this report, we present an infant with Acremonium spp. peritonitis. A 7-month-old boy with Down syndrome, congenital heart disease, pulmonary hypertension and congestive heart failure required peritoneal dialysis for his persistent pulmonary oedema and symptomatic hyponatremia. Acremonium spp. peritonitis developed while he was on extended spectrum antibiotics and fluconazole. The patient was successfully treated with peritoneal dialysis catheter removal and liposomal amphotericin B. The case was presented to draw attention to a rare cause of peritonitis -Acremonium spp. - in a paediatric patient.