Galina Balakirski

Chronic spontaneous urticaria and internal parasites – a systematic review

Chronic spontaneous urticaria (CSU) is defined as persistent wheals, angioedema, or both lasting for >6 weeks due to known or unknown causes. Some epidemiological studies and case reports suggest that internal parasite infections (PI) can cause CSU. Here, we provide a systematic overview of published findings on the prevalence and relevance of PI in CSU and we discuss possible pathomechanisms. The prevalence of PI in CSU was investigated by 39 independent studies and comorbidity reportedly ranged from 0 to 75.4% (two‐thirds of these studies reported infection rates of 10% or less). The prevalence of PI in adult and pediatric CSU patients ranged from 0% to 75.4% and from 0% to 37.8%, respectively. CSU patients were more often diagnosed with protozoa and had a significantly higher risk of toxocariasis seropositivity and Anisakis simplex sensitization when compared to healthy controls. Patients with chronic urticaria more frequently had seropositivity of fasciolosis, Anisakis simplex sensitization, and the presence of Blastocystis hominis allele 34 (ST3) as compared with control subjects. In 21 studies, efficacy of treatment with antiparasitic drugs ranged from 0 to 100% (35.7% of 269 CSU patients benefitted). In 9 (42.8%) of 21 studies, more than 50% of efficacy was observed. The reported rate of urticaria comorbidity in PI patients in 18 independent studies is 1–66.7%. Urticaria including CSU might be a quite common symptom of strongyloidiasis and blastocystosis. Pathogenic mechanisms in CSU due to PI may include specific IgE, Th2 cytokine skewing, eosinophils, activation of the complement, and the coagulation systems.

Potential health risk of allergenic pollen with climate change associated spreading capacity: Ragweed and olive sensitization in two German federal states.

BACKGROUND Global climate changes may influence the geographical spread of allergenic plants thus causing new allergen challenges. OBJECTIVE Allergy patients from two German federal states were compared for their status quo sensitization to ragweed, an establishing allergen, olive, a non-established allergen, and the native allergens birch, mugwort, and ash. METHODS Between 2011 and 2013, 476 adult allergy patients per region were recruited. Patients completed a questionnaire, participated in a medical interview, and underwent skin prick testing and blood withdrawal for analysis of specific IgE to allergen components (ISAC technology). Data on regional pollen load from 2006 to 2011 were acquired from the German Pollen Information Service Foundation. RESULTS Prick test reactivity to ragweed and ash, respectively, was lower in Bavaria than in NRW (ragweed: p=0.001, aOR=0.54; ash: p=0.001, aOR=0.59), whereas prick test reactivity to olive was higher (p=0.000, aOR=3.09). Prick test reactivity to birch and mugwort, respectively, did not significantly differ. 1% (1/127) of patients with prick test reactivity to ragweed showed sIgE to Amb a 1, and 65% (86/132) of olive-but-not-ash reactive patients showed sIgE to Ole e 1 (NRW: 67%, Bavaria: 65%; p=0.823, OR=0.91). Regional differences in sensitization pattern were neither explainable by cross-reactivity to pollen pan-allergens nor non-exposure variables nor by reported plant population or pollen data. CONCLUSIONS Spread of ragweed and particularly olive may result in prompt occurrence of allergic symptoms. Early identification of invasive allergens due to climate change does need time and spatial close meshed measurement of respective indicator allergens and sensitization pattern.

Cutaneous allergic drug reactions: update on pathophysiology, diagnostic procedures and differential diagnosic

Abstract Important changes in the understanding and management of drug hypersensitivity reactions during the last years result from the increasing importance of biologics in medical practice, which differ in their spectrum of adverse drug reactions (ADRs) from the classical covalent drugs. With regard to covalent drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause of anaphylactic and photosensitivity reactions. Especially in allergic reactions to NSAIDs, pseudoallergic reactions should be considered in the differential diagnosis. In opposite to the main cutaneous allergic drug reactions such as urticaria or maculopapular skin rash, in which antibiotics are the main culprits, in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN (Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are the main causes. Similar mutations in the IL36R gene, which were found in both patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular psoriasis, make the differential diagnosis more difficult and raise the question whether there is a difference between these diseases or whether AGEP is not just a drug induced pustular psoriasis. Finally, some special aspects of side effects of biologics and targeted therapies respectively are discussed.

[Bullous pemphigoid: a new look at a well-known disease].

BACKGROUND Bullous pemphigoid is an autoimmune blistering disease that is associated with appearance of subepidermal blisters. IgG antibodies against components of the epithelial basement membrane (BP 180 and 230 antigens) can be typically found in serum of patients. Direct immunofluorescence reveals usually a linear deposition of IgG and/or C3 along the basement membrane, but other immunoglobulins may also be present. CASE PRESENTATION Our patient had no detectable formation of tense blisters of his skin; instead, the clinical picture was rather compatible with a prurigo simplex subacuta or a pruritic variant of atopic dermatitis. He also had a markedly elevated total serum IgE level. The diagnosis was confirmed by detection of circulating IgG against BP 180 in patients serum in ELISA and detection of linear IgG deposits along the basement membrane zone of epidermis in the direct immunofluorescence. CONCLUSION Atypical clinical presentations of bullous pemphigoid without blister formation are possible. Recent studies show that an increased total IgE level in serum of patients may occur frequently. The aim of this report is to provide the reader with a brief insight in the new findings in pathogenesis and therapy of bullous pemphigoid.

Effectiveness and Safety of Surgical Excision in the Treatment of Digital Mucoid Cysts

BACKGROUND Digital mucoid cysts have a tendency for recurrence after operative intervention. Several procedures are in use. OBJECTIVE Retrospective evaluation for effectiveness, safety and patient satisfaction by using a questionnaire after treatment for digital mucoid cysts with targeted surgical excision and closure by flap-design. MATERIALS AND METHODS All patients treated with surgical excision for digital mucoid cysts at the Dermatology Department of the Ludwigshafen City Hospital between 2007 and 2011 were evaluated using a specially designed questionnaire. RESULTS We evaluated 31 patients. The patient group consisted of 65% women, the median age was 61 years. Seventy-eight percent of patients with nail involvement had a marked improvement or complete resolution of this complaint after surgery. A few complications (e.g., redness, pain or hematoma) were observed after treatment, but no patients required oral antibiotics. Patient evaluation of cosmetic outcome revealed high satisfaction with the procedure, nevertheless recurrence of the digital mucoid cysts was observed in 22.5% of all cases. CONCLUSION Surgical excision in treatment of digital mucoid cysts was shown to be effective and safe. However, possible advantages and disadvantages of this treatment option should be discussed with the patients before a decision on the kind of therapy is reached.

The effects of zinc- and copper-containing welding fumes on murine, rat and human precision-cut lung slices

Recently, the pro-inflammatory effects of metal inert gas brazing welding fumes containing zinc and copper have been demonstrated in humans. Here, murine, rat and human precision cut lung slices (PCLS) were incubated in welding fume containing media with 0.1, 1, 10 and 100 μg/ml for 24 or 48 h. 24 h incubation were determined either by incubation for the total time or for only 6 h followed by a 18 h post-incubation phase. Cytotoxicity, proliferation and DNA repair rates, and cytokine levels were determined. Welding fume particle concentrations of 0.1 and 1 μg/ml showed no toxic effects on PCLS of all three species, while for 10 and 100 μg/ml a concentration-dependent toxicity occurred. Proliferation and DNA repair rates were reduced for all tested concentrations and incubation times. Additionally, the cytokine levels in the supernatants were markedly reduced, while after 6 h of exposure with 18 h of post-incubation time a trend towards increased cytokine levels occurred. PCLS are a reliable and feasible method to assess and offer a prediction of toxic effects of welding fume particles on human lungs. Rat PCLS showed similar responses compared to human PCLS and are suitable for further evaluation of toxic effects exerted by welding fume particles.

Individual risk assessment in the diagnosis of immediate type drug hypersensitivity reactions to betalactam and non-betalactam antibiotics using basophil activation test: a single center experience

Abstract Background: Drug hypersensitivity reactions of immediate type pose a challenging problem, especially, if standard diagnostic procedures do not lead to conclusive results. The aim of this investigation is to identify, whether basophil activation test (BAT) is able to provide additional benefit in the diagnostic evaluation of immediate type drug hypersensitivity reactions to antibiotics in comparison with the routine allergological diagnostic methods. Materials and methods: We investigated patients, who presented to the Department of Dermatology and Allergology of the University Hospital of RWTH Aachen in Germany for diagnostic workup of type I allergic reactions to antibiotics during the period from 2009 to 2012. The analysis was performed retrospectively based on patient records. The inclusion criteria were performed standard allergological in vivo diagnostic and a BAT as a part of diagnostic workup. Results: Eighty-two diagnostic investigations were performed in 52 patients. BAT was positive in 9 of 12 cases with a positive clinical history but negative skin test results. Furthermore, all patients who reported severe drug hypersensitivity reactions (anaphylactic reaction grade 2 and above) showed positive BAT (5/5), while only three of these five cases demonstrated a positive skin testing that led to the conclusion of possible immediate type drug hypersensitivity. Conclusions: Although skin tests remain the most important part of the primary diagnostic investigation, BAT is an additional valuable and sensitive in vitro test in the diagnostic procedure of immediate type allergic reactions to antibiotics. However, further standardized investigations are needed in order to calculate exact sensitivity and specificity of this diagnostic tool in both, adult and pediatric populations.

Juvenile pityriasis rubra pilaris: successful treatment with methotrexate

A 3-year-old girl presented with a 1-month history of a generalized pruritic rash. The child had been born at full term with a normal birth weight, and she was otherwise healthy, with no known allergies and she had received all vaccinations. There was no family history of rashes. On physical examination, the patient was found to have scaly, reddish to orange plaques with islands of spared skin (nappes claires) and prominent erythematous follicular papules at the margins (Fig. 1a–d). The palms and soles were also affected. Results of laboratory blood and urine investigations were unremarkable. Histopathological examination of biopsies from the lesions showed orthokeratosis alternating with parakeratosis, a slightly acantholytic epidermis with normal granular layer, and a sparse perivascular and superficial inflammatory infiltrate of lymphocytes (Fig. 1e). A diagnosis of pityriasis rubra pilaris (PRP) was made, and the patient was commenced on systemic therapy with oral methotrexate (MTX) 5 mg/week (about 2.5 mg/kg body weight for a body weight of 18.5 kg), increased to 7.5 mg (about 0.4 mg/kg body weight) 3 weeks later, which she tolerated well. Results of routine monitoring of blood count, renal function parameters, liver transaminases and gammaglutamyltransferase werre normal. Urea-containing emollients were used for topical treatment. The patient had marked improvement within 1 month of the therapy starting, which is the usual time frame in which MTX also shows effectiveness in juvenile idiopathic arthritis, and complete remission was achieved with 3 months of the treatment (Fig. 2a–c), thus the systemic therapy was discontinued. No recurrence of disease was seen at monthly follow-up visits over a period of 6 months. PRP is a rare papulosquamous skin disease of unknown aetiology. It mostly affects patients in the first decade and the fifth to sixth decades of life. It has an equal sex predilection. The diagnosis is made clinically and confirmed histologically. Based on the classification proposed by Griffiths, six types of PRP can be distinguished: classic adult PRP (Type I) with generalized skin involvement and mostly spontaneous remission within 3–5 years; atypical adult (Type II) with generalized lesion distribution, but chronic disease course; juvenile classic (Type III), which is similar to Type I in clinical presentation, but occurs during the first years of life; juvenile circumscribed (Type IV), which has localized skin involvement, but unpredictable prognosis; juvenile atypical (Type V), which has a clinical pattern similar to that of Type III, but is chronic and intractable; and human immunodeficiency virus-associated (Type VI). In the past few years, acute bacterial infections have been discussed as a possible trigger of PRP. In our case, juvenile classic PRP (Type III) was diagnosed. Spontaneous resolution of the disease after months or years has been reported. However, treatment should be considered in order to improve the patient’s quality of life even if data on successful therapy is limited. Retinoids (isotretinoin, acitretin and etretinate) represent the most described treatment in both children and adults, but one of the possible severe side effects of these treatments in children is Correspondence: Dr Abdullah Alazemi, Department of Dermatology and Allergology, Universitiy Hospital of RWTH Aachen Pauwelsstr. 30, 52074 Aachen, Germany E-mail: dr.alazemi@hotmail.com

Triple metal-hypersensitivity in the patient with knee prosthesis: a rare case

Case presentation A 70-years old healthy male patient presented in our clinic with a recurrent swelling, redness and limitation of movement of his right knee. Clinical examination and laboratory findings showed no evidence of bacterial infection of the joint. The patient had no other complaints. According to the clinical history the patient received titanium prosthesis of the right knee in 2009. One year later he developed swelling, redness and limitation of movement of this joint. The patient reported also about a skin patch test that was performed and was positive for titanium. However there is no documentation available. In 2011 the prosthesis of the right knee was replaced by a CoCrMo/FeCrNiMnMoNbN/UHMWPE knee prosthesis due to persistent signs and symptoms. During the initial period of 6 months the patient reported to be free of complaints, but after this period he developed symptoms again. A CT-Scan of the right knee was unremarkable. The new skin patch test was positive for cobalt(II)chlorid (CoCl2) and potassium dichromate (K2Cr2O7). Five months later the skin patch test was repeated, but no reaction to CoCl2 or K2Cr2O7 was seen. The diagnosis remained questionable.

Doppelsensibilisierung auf PR-10- und PR-14-Proteine@@@Double sensitization to PR10 and PR-14 proteins

ZusammenfassungEine Patientin mit bekanntem oralem Allergiesyndrom auf Haselnüsse und Pfirsiche entwickelte eine Anaphylaxie nach Verzehr von Haselnüssen und Pfirsichen. Obschon Anaphylaxien auf Bet-v1-Homologe beschrieben sind, zeigte sich in der weiteren Diagnostik eine Sensibilisierung auf Lipidtransferproteine, die für ihre schwereren Reaktionen bekannt sind. Doppelsensibilisierungen auf sowohl PR-10- als auch PR-14-Proteine sollten mit untersucht werden und scheinen auch in unseren Breitengraden zunehmend bekannt zu werden.AbstractA patient with mild oral allergy syndrome presented with a history of anaphylaxis induced by both hazelnuts and peaches. The ensuing work-up showed a double sensitization to proteins in both pathogenesis-related group 10 (e.g. Bet v1, Cor a1, Pru p1) and 14 (e.g. Pru p3, Cor a8). Such double sensitization profiles are increasingly being recognized in Europe.A patient with mild oral allergy syndrome presented with a history of anaphylaxis induced by both hazelnuts and peaches. The ensuing work-up showed a double sensitization to proteins in both pathogenesis-related group 10 (e.g. Bet v1, Cor a1, Pru p1) and 14 (e.g. Pru p3, Cor a8). Such double sensitization profiles are increasingly being recognized in Europe.