[Acute hypersensitivity reactions associated with monoclonal antibodies for targeted therapy]. / Akute Überempfindlichkeitsreaktionen auf monoklonale Antikörper zur zielgerichteten Therapie.

The application of biologics such as monoclonal antibodies for targeted therapy may lead to immediate adverse drug reactions with different pathophysiological mechanisms. Some of them are due to the immunogenicity of these drugs and are truly allergic, some of them are non-allergic, some are on-target, and some are off-target. The main example of non-allergic reactions are infusion reactions, mainly induced by cytokine release. They generally occur already at the first application and symptoms may decrease in subsequent applications. Allergic reactions need a preceding sensitization phase and therefore may not occur at first application. However, if the IgE-mediated reaction is due to cross-reactivity, they may occur at the first application of the monoclonal antibody. The management of these reactions depends on their severity and the ultimate need to treat the patient with these drugs.

[Lichenoid drug reactions]. / Lichenoide Arzneimittelreaktionen.

Lichenoid drug reactions are rare compared to typical morbilliform drug exanthema or urticaria. They are associated with specific drugs or drug families like gold, antimalarial drugs, ß­blockers and angiotensin-converting-enzyme inhibitors. Recent observations included associations with novel drugs such as biologics (e. g. tumour necrosis factor antagonists) and immune checkpoint inhibitors (anti-programme cell death protein 1 antibodies). Lichenoid drug reactions most often resemble lichen planus mainly in areas of ultraviolet-light exposed skin, but also mucosal lichen planus and even bullous lesions may occur.

Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: report of two cases and review of literature.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is characterized by formation of subepidermal bullae due to functional disturbance of the hemidesmosomal proteins on the keratinocytes at the basal membrane zone. In recent years, several studies have emphasized the important role of IgE autoantibodies in the pathogenesis of BP. Consequently, a therapeutic approach using IgE depleting antibodies, such as a humanized monoclonal anti-IgE antibody (e.g. omalizumab) may represent a new option for treatment of this autoimmune disease. METHODS: In this paper, we report about the successful treatment of BP with omalizumab in two patients and provide a review of the current literature on the relationship between IgE antibodies and this autoimmune blistering disease. RESULTS: Two patients with therapy-resistant BP were treated with humanized monoclonal anti-IgE antibody omalizumab 300 mg subcutaneously every 3 weeks as corticosteroid-sparing agent. Under this therapy, both patients experienced a significant improvement of skin condition and almost complete resolution of pruritus. The treatment was well tolerated. CONCLUSION: Until recently IgG autoantibodies against the basal membrane proteins BP180 und BP230 were considered to be causative in the pathogenesis of BP. However, new in vitro studies as well as data from experimental mouse models have indicated that in addition to specific IgG, also IgE antibodies against BP180 and BP230 play a role in the development of this disease. Based on these new findings, new treatment modalities of BP became possible.

[Porphyria cutanea tara]. / Porphyria cutanea tarda.

Porphyria cutanea tara (PCT) has a prevelance of about 40 new diagnoses per 1 million people per year and is the most frequently occurring type of porphyria worldwide. Inhibition of the uroporphyrinogen decarboxylase (UROD) is the main cause of the disease, which can be the result of a heterozygous or homozygous mutation of the UROD gene; however, xenobiotics or other diseases may play an important role for the precipitation of the disease. Risk factors include alcohol, estrogen, iron overload, and hemochromatosis, hepatitis C or poisoning, e.g., with polyhalogenated aromatic compounds such as hexachlorobenzene. Signs and symptoms are blisters, skin fragility, erosions hyperpigmentation, sclerodermoid plaques. Therapy includes sun protection, prevention of risk factors, phlebotomy, and chloroquine.

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.

[Bullous pemphigoid: a new look at a well-known disease]. / Bullöses Pemphigoid: Ein neuer Blick auf eine bekannte Krankheit.

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 patient's 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.

[Double sensitization to PR10 and PR-14 proteins]. / Doppelsensibilisierung auf PR-10- und PR-14-Proteine.

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.

[Post-vaccination granulomas caused by delayed-type reaction to aluminum salts]. / Impfgranulom bei Spättypallergie gegen Aluminiumsalze.

BACKGROUND: Aluminium salts are common adjuvants in all established inactivated vaccines. They are necessary to activate the humoral immune system. In the 1990s a Swedish study on an acellular vaccination against pertussis was started. Until 2013, 745 of 760,000 children with pruritic subcutaneous nodules were identified. In 77 % of these children a contact allergy to aluminium could be proven. Contact allergy to aluminium induced by vaccines causes pruritic subcutaneous nodules at the vaccination site. During infections of the upper respiratory tract the pruritus often escalates with inflammatory, erythematous and urticarial plaques. CONCLUSIONS: The use of solutions containing aluminium salts for specific immunotherapy is contraindicated in the case of contact allergy to aluminium. Intramuscular injections of inactivated vaccines can be employed to avoid granuloma formation.

Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate.

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ± 0.1%. For improved preclinical evaluation, we combined tissue engineering with clinically used keratin-18 quantification. Three doses of 10(-3) mol/l OxBu, dissolved in phosphate-buffered saline as well as loaded to SLN, were effective on reconstructed NMSC. Tumour response and apoptosis induction were evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7 activation as well as by reduced expression of matrix metallopeptidase-2 and Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and thus the drug should be subjected to the next step in preclinical evaluation.

[Retinoids in dermatopharmacology]. / Retinoide in der Dermatopharmakologie.

BACKGROUND: Retinoids are important in regulating cell proliferation and differentiation and play an important role in the body, including the skin. OBJECTIVES: Our objective is to review the current medical literature regarding use, effects and side-effects of topical and systemic retinoids used for therapy. METHODS: Pubmed/Medline electronic database was searched for relevant German and English literature. RESULTS: The group of retinoids used for therapeutic purposes includes both naturally occurring and chemically synthesized vitamin A derivates. Because of their influence on keratinization and epithelial differentiation, as well on the proliferation of benign and malignant keratinocytes, retinoids have found a wide application in the field of dermatopharmacology. CONCLUSION: Retinoids are among the most efficacious drugs used in the treatment of dermatological disorders and have a wide range of biological effects. Thorough knowledge about side-effects and comprehensive information for the patient are essential for safe treatment with retinoids.

Molecular microarray analysis reveals allergen- and exotoxin-specific IgE repertoires in children with atopic dermatitis.

BACKGROUND: Children suffering from atopic dermatitis frequently show allergen-specific sensitization. However, the corresponding IgE-recognition patterns have not yet been extensively characterized using multiallergen microarrays. OBJECTIVE: To provide comprehensive, molecular IgE repertoires in paediatric patients with atopic dermatitis using microarray technology. METHODS: Sera of 140 affected children were screened with a protein microarray containing a panel of 95 inhalant, food and staphylococcal antigen components. In addition, total serum IgE levels and further clinical parameters were recorded. RESULTS: At a mean total IgE level of 1528 kU/L, the number of sensitizations varied from 0 to 32 per patient, and regression analysis revealed a significant association between total IgE and the quantity of recognized antigens. A total of 78 single allergen and microbial components elicited at least one IgE response, while 11 plant and 13 non-plant molecules were recognized by more than 10% of patients. Specific IgE against Staphylococcus aureus could be detected in 14% of children. Sensitization rates against the studied allergen molecules differed significantly when stratified by age. Whereas reactivity against inhalant allergens and SEC was lowest in the youngest group (<24 months) reaching highest values in children ≥ 72 months, IgE responses against food allergen components peaked in younger age groups (0-48 months) and clearly declined in patients of higher age. The large amount of microarray data could be aggregated by centroid cluster analysis revealing valid allergen clusters possibly linked with higher disease severity as determined by multivariate analysis of covariance. CONCLUSION: Allergenic molecule microarray analysis can be regarded as a suitable research tool for large-scale IgE screening in infants and children with atopic dermatitis (AD). Still, further studies in well-defined populations are needed to exactly identify its tangible benefits in the diagnostic and therapeutic management of affected patients in daily clinical practice.

[Anaphylaxis to PR-10 proteins (Bet v1 homologues)]. / Anaphylaxie auf PR-10-Proteine (Bet v1-Homologe).

Secondary food allergies to PR-10 proteins (Bet v1 homologues) are the most common food allergies in Germany. Clinically they present with an oral allergy syndrome (intraoral pruritus and perhaps swelling). When drinks containing PR-10 proteins are rapidly consumed, for example after sporting activities, large concentrations of allergen can be reached without any intraoral symptoms and then lead to anaphylaxis. This phenomenon has often been described for soja milk and occurred in our case with an apple drink with 60% fruit concentration. It seems likely that such cases of anaphylaxis are not adequately represented in the anaphylaxis registry.

[Alopecia areata]. / Alopecia areata.

The epidemiology of alopecia areata as well as murine models of this disease and genome-wide association studies support the concept of alopecia areata as an autoimmune disease. In addition, the genome-wide association studies have led to the identification of new potential therapeutic targets such as CTLA4; these results have already led to the initiation of clinical studies, for example, with abatacept. Currently topical and intralesional corticosteroids as well as immunotherapy with diphenylcyclopropenone are most common therapeutic approaches.

[Eccrine poroma]. / Ekkrines porom.

A 42-year-old man presented with a rapidly growing nodule on his right cheek. Except for some itching, it was asymptomatic. The tumor was excised with 3-4 mm safety margin. The clinical differential diagnostic considerations included pyogenic granuloma, amelanotic melanoma, basal cell carcinoma and eccrine poroma. An eccrine poroma is a rare tumor derived from the eccrine sweat gland. Hormonal disturbances, trauma, immunosuppression, actinic damages and radiotherapy have been suggested as possible etiologic factors; however, the exact pathophysiology remains unclear.

[Value of in-vitro diagnostic tools after anaphylaxis]. / Stellenwert der In-vitro-Diagnostik nach Anaphylaxie.

Anaphylaxis is a potentially life-threatening reaction and should be treated immediately. Diagnosis is made based on history and clinical features. However, measurement of sequential serum tryptase can provide additional clues and should be performed soon as possible. Referral to specialist allergy service is believed to reduce rate of recurrence. New specific in vitro techniques to indentify the triggering agent help optimize secondary preventive measures. Thus in vitro diagnosis plays an important, albeit complementary, role both in the acute and secondary phases facilitating a safe diagnosis and aiding in the overall management of the disease.