Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome.

BACKGROUND: Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders. METHODS: Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed. RESULTS: All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999). CONCLUSIONS: The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.

[Intertriginous psoriasis]. / Psoriasis intertriginosa.

Intertriginous psoriasis is a variant of psoriasis that is associated with inflammatory lesions in skin folds. Patients often feel ashamed, are subjected to stigmatization, social isolation, or experience mental health issues. There is no general consensus on the definition of intertriginous psoriasis. Depending on the definition used, the prevalence varies substantially. Due to the particular location of skin lesions, therapeutic management is very challenging. Mild symptoms can be treated with topical corticosteroids or topical immunomodulators. There are encouraging data demonstrating the efficacy of ixekizumab, possibly charting the way for it to become a systemic treatment option.

[Seasonal and Perennial Allergic Rhinoconjunctivitis]. / Die saisonale und perenniale allergische Rhinokonjunktivitis.

Seasonsal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) as well as intermittent and persistent allergic rhinitis are widespread diseases. Because a combined occurrence of ocular and nasal symptoms is very common the summarising term allergic rhinoconjunctivitis is frequently used. SAC and PAC representing the two acute forms of allergic conjunctivitis account for more than 90% of all cases of allergic conjunctivitis. Compared to the chronic forms of allergic conjunctivitis their course of disease is milder. Nevertheless because of their high prevalence and the proven influence on patients' quality of life they possess clinical and socioeconomic relevance. Allergic rhinoconjunctivitis is caused by a type 1 IgE-mediated hypersensitivitity reaction that is provoked by aeroallergens in the majority of cases. The pathognomonic sign is itching. Besides, typical ocular findings are chemosis, conjunctival injection,watery secretion and lid swelling. Otorhinolaryngologists' findings include rhinorrhea, postnasal drip and sneezing. Problems in breathing through the nose resulting from nasal obstruction can cause impaired nighttime sleep and daytime somnolence. In addition to a reduction of allergen exposure by modification of environment and life style factors, in mild forms of SAC and PAC artificial tears are recommended. Topical antihistamines can generate rapid relief from acute symptoms and itching. Topical mast cell stabilisers however provide long-term effects. Dual action drugs that combine antihistamines and mast cell stabilisers show increased patient compliance due to reduced application frequency. Use of topical steroids should be cautious and only temporary. For prolonged treatment periods unpreserved anti-allergic eye-drops should be preferred. Combined topical antihistamines and new-generation topical nasal steroids often used by otorhinolaryngologists demonstrate a good safety profile without systemic side effects. In summary, allergic rhinoconjunctivitis represents a common disease pattern that can be treated effectively. Once it is diagnosed correctly targeted treatment results in improved patients' quality of life quickly.

Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

[Successful treatment of pediatric psoriasis with etanercept]. / Erfolgreiche Therapie mit Etanercept bei Psoriasis im Kindesalter.

Systemic treatment options for moderate to severe pediatric psoriasis are limited. Due to uncertainties regarding severe adverse events the majority of established systemic therapeutic drugs for adult psoriasis are not administered to children. In 2011 the TNF-α-inhibitor etanercept (Enbrel(®)) was approved as the first biological agent for the treatment of plaque psoriasis in pediatric patients. It is available for children from the age of 6 years and constitutes an effective and safe treatment option during childhood. Our report is based on the successful treatment of three boys with etanercept each at the age of 11 years.

[Successful drug desensitization after vemurafenib-induced rash]. / Erfolgreiche Medikamentendesensibilisierung nach Vemurafenib-induziertem Arzneimittelexanthem.

The BRAF inhibitor vemurafenib was approved in 2011 for the treatment of inoperable or metastatic melanoma. Vemurafenib therapy is associated with several side effects, such as arthralgia, secondary skin tumors or inflammatory rashes. In particular cutaneous toxicities represent a serious threat to patients' adherence. Here, we present the case of a successful drug desensitization in a patient that presented with a vemurafenib-induced rash. Lymphocyte activation tests failed to detect drug-specific T cells, suggesting that the development of the rash was based upon a nonallergic drug hypersensitivity reaction. A program of slow desensitization was initiated and subsequently, vemurafenib was tolerated at the full effective and recommended dosage.

[Juvenile systemic lupus erythematosus with unusual manifestation of lupus-associated panniculitis]. / Juveniler systemischer Lupus erythematodes mit der ungewöhnlichen Manifestation einer Lupus-assoziierten Pannikulitis.

Juvenile systemic lupus erythematosus (JSLE) is a rare multisystem autoimmune disease with broad heterogeneity of clinical manifestations. Diagnosing JSLE is often very challenging. This life-threatening, unpredictable, and relapsing disease, which may affect various organ systems, requires interdisciplinary, lifelong care. Here, we report the case of a 13-year-old patient with JSLE suffering from recurrent arthralgia, lupus panniculitis, and rashes that were successfully treated with hydroxychloroquine and prednisolone.

[Acquired angioedema with C1-INH deficiency and accompanying chronic spontaneous urticaria in a patient with chronic lymphatic B cell leukemia]. / Erworbenes Angioödem mit C1-INH-Defizienz und begleitender chronisch spontaner Urtikaria bei chronisch lymphatischer B-Zell-Leukämie.

Acquired angioedema due to C1 inhibitor deficiency (C1-INH-AAE) is characterized by recurrent edema of the subcutaneous and/or submucosal tissue without wheals and negative family history of angioedema. Here, we present the case of a patient with a chronic lymphatic B cell leukemia who suffered from both C1-INH-AAE and chronic spontaneous urticaria. Oral corticosteroids, antihistamines, and the anti-IgE antibody omalizumab were applied to treat the chronic urticaria in combination with the plasma-derived C1 esterase inhibitor concentrate Berinert® and the bradykinin B2 receptor antagonist icatibant, but the symptoms did not improved significantly. Thus, polychemotherapy targeting the slow-growing lymphoproliferative disease including rituximab was initiated, which resulted in remission of both the urticaria and the angioedema.

Can we say what diet is best for health?

Diet is established among the most important influences on health in modern societies. Injudicious diet figures among the leading causes of premature death and chronic disease. Optimal eating is associated with increased life expectancy, dramatic reduction in lifetime risk of all chronic disease, and amelioration of gene expression. In this context, claims abound for the competitive merits of various diets relative to one another. Whereas such claims, particularly when attached to commercial interests, emphasize distinctions, the fundamentals of virtually all eating patterns associated with meaningful evidence of health benefit overlap substantially. There have been no rigorous, long-term studies comparing contenders for best diet laurels using methodology that precludes bias and confounding, and for many reasons such studies are unlikely. In the absence of such direct comparisons, claims for the established superiority of any one specific diet over others are exaggerated. The weight of evidence strongly supports a theme of healthful eating while allowing for variations on that theme. A diet of minimally processed foods close to nature, predominantly plants, is decisively associated with health promotion and disease prevention and is consistent with the salient components of seemingly distinct dietary approaches. Efforts to improve public health through diet are forestalled not for want of knowledge about the optimal feeding of Homo sapiens but for distractions associated with exaggerated claims, and our failure to convert what we reliably know into what we routinely do. Knowledge in this case is not, as of yet, power; would that it were so.

[Current status of oral immunomodulatory and immunosuppressive agents]. / Aktueller Stand der oralen Therapie mit immunmodulatorischen und immunsuppressiven Medikamenten.

Various dermatological disorders require treatments with immunosuppressive or immunomodulatory agents. Nevertheless, several studies demonstrate low prescription rates for systemic treatments. This low usage may be a result of physicians' low levels of confidence in administering systemic treatments. However, immunosuppressive treatments represent safe options when potential side effects as well as pharmacological interactions are considered. This review overviews the most important oral immunosuppressive or immunomodulatory agents and summarizes their mode of actions, indications, and adverse effects. Biologics that require intravenous or subcutaneous application are not included, but novel and new agents likely to be released soon are considered.

[Eosinophilic granulomatosis with polyangiitis presenting as livedo racemosa]. / Livedo racemosa als kutane Manifestation bei eosinophiler Granulomatose mit Polyangiitis.

As a rare antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is characterized by asthma, severe peripheral eosinophilia and the presence of extravascular granulomas. Cutaneous involvement usually includes palpable purpura or cutaneous to subcutaneous nodes. We present the case of a 43-year-old woman with EPGA and the unusual cutaneous manifestation of livedo racemosa.

[Seasonal and perennial allergic rhinoconjunctivitis]. / Die saisonale und perenniale allergische Rhinokonjunktivitis.

Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) as well as intermittent and persistent allergic rhinitis are widespread diseases. Because a combined occurrence of ocular and nasal symptoms is very common the summarising term allergic rhinoconjunctivitis is frequently used. SAC and PAC representing the two acute forms of allergic conjunctivitis account for more than 90 % of all cases of allergic conjunctivitis. Compared to the chronic forms of allergic conjunctivitis their course of disease is milder. Nevertheless because of their high prevalence and the proven influence on patients' quality of life they possess clinical and socioeconomic relevance. Allergic rhinoconjunctivitis is caused by a type 1 IgE-mediated hypersensitivity reaction that is provoked by aeroallergens in the majority of cases. The pathognomonic sign is itching. Besides, typical ocular findings are chemosis, conjunctival injection, watery secretion and lid swelling. Otorhinolaryngologists' findings include rhinorrhea, postnasal drip and sneezing. Problems in breathing through the nose resulting from nasal obstruction can cause impaired nighttime sleep and daytime somnolence. In addition to a reduction of allergen exposure by modification of environment and life style factors, in mild forms of SAC and PAC artificial tears are recommended. Topical antihistamines can generate rapid relief from acute symptoms and itching. Topical mast cell stabilisers however provide long-term effects. Dual action drugs that combine antihistamines and mast cell stabilisers show increased patient compliance due to reduced application frequency. Use of topical steroids should be cautious and only temporary. For prolonged treatment periods unpreserved anti-allergic eye-drops should be preferred. Combined topical antihistamines and new-generation topical nasal steroids often used by otorhinolaryngologists demonstrate a good safety profile without systemic side effects. In summary, allergic rhinoconjunctivitis represents a common disease pattern that can be treated effectively. Once it is diagnosed correctly targeted treatment results in improved patients' quality of life quickly.

[Successful treatment of granulomatous rosacea with dapsone]. / Erfolgreiche Therapie einer granulomatösen Rosazea mit Dapson.

Granulomatous rosacea is an uncommon variant of rosacea. It is characterized by disseminated, red-brown papules and nodules especially in periocular and centrofacial locations. This form of rosacea causes considerable distress among patients because of the inflammatory facial lesions and represents a therapeutic challenge. A 62-year old man with granulomatous rosacea failed to improve with systemic doxycycline. Systemic isotretinoin and corticosteroids produced only a temporary reduction in cutaneous findings. Finally, systemic treatment with dapsone resulted in remission of the skin lesions and long-term stabilization.

[Fiddler's neck]. / Geigerknoten.

The fiddler's neck is an uncommon variant of acne mechanica in violinists and violists. It is a single firm red-brown dermal nodule usually on the left side of neck. This special form of acne mechanica represents a therapeutic challenge since the triggering mechanical factors persist, unless they can be corrected by changes in positioning or modifications of the chin pad. A 72-year-old woman who had played the violin since childhood presented with a red-brown nodule on her neck for 18 months. Cushioning provided no relief. Excision of the affected area with primary closure represented one therapeutic option. Further supportive measures include improved posture to reduce the pressure between skin and instrument and interposing a neck cloth.

Unilateral decrease in inner ear signal in fluid-attenuated inversion recovery sequences in previously suspected canine idiopathic vestibular syndrome.

The aetiology of canine idiopathic vestibular syndrome (IVS) remains unclear. In human medicine, characteristic magnetic resonance imaging (MRI) techniques are used to demonstrate differences in endolymph composition between affected and unaffected inner ears. The purpose of this study was to determine whether similar MRI techniques could help to detect changes in the inner ears of canine IVS patients. Medical records from two veterinary referral clinics were reviewed retrospectively. Dogs were included if they had a diagnosis of IVS, obvious lateralisation of clinical signs, and an MRI of the vestibular system. A region of interest (ROI) was manually outlined by defining the anatomical area of the inner ear in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. In order to calculate the ratio of FLAIR suppression of each ear, the mean grey value of the ROI was determined in both sequences. If a unilateral decrease in suppression was identified, it was compared with the direction of clinical signs. In total, 80 dogs were included in the study. There was a significantly lower degree of suppression on the affected compared to the unaffected side (0.8886 vs. 0.9348, respectively; P = 0.0021). In 92.5% of cases, there was agreement between the most suppressed side on MRI and the direction of clinical signs. This study provides preliminary evidence about the appearance of endolymph on MRI of dogs with IVS. Further studies are needed to investigate associations between the severity of MRI changes and prognosis.

[Seasonal allergic conjunctivitis]. / Saisonale allergische Konjunktivitis.

Seasonal allergic conjunctivitis (SAC) is a frequent disease, which is often associated with allergic rhinitis and subsequently manifested as allergic rhinoconjunctivitis. In contrast to other types of chronic allergic conjunctivitis, the course of SAC is not sight-threatening. Pathogenetically, the underlying cause of SAC is an immunoglobulin E (IgE) mediated, Th2-driven type 1 hypersensitivity reaction. Clinically it presents with itching, light-red conjunctival injection as well as chemosis that exceeds the extent of conjunctival injection. The goals of treatment are relief of acute signs and symptoms, control of the underlying inflammatory process and utilization of preventive options. Dually effective local therapeutics combine the advantages of rapid action with a relatively long-lasting effect by a two-fold active approach. Specific immunotherapy is useful in selected patients.