Cornelia S. Seitz

Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

IntroductionIn the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry.MethodsSera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion.ResultsAntinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged.ConclusionsThis study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients.

Diagnostic testing in suspected fluoroquinolone hypersensitivity

Background Because of their broad antibacterial activity in the gram‐negative and gram‐positive spectrum, high oral bioavailability, and good tissue penetration, fluoroquinolone antibiotics are widely used. Besides direct drug‐related side‐effects, fluoroquinolones may cause hypersensitivity reactions.

Diagnosis of drug hypersensitivity in children and adolescents: Discrepancy between physician‐based assessment and results of testing

To cite this article: Seitz CS, Bröcker E‐B, Trautmann A. Diagnosis of drug hypersensitivity in children and adolescents: Discrepancy between physician‐based assessment and results of testing. Pediatric Allergy Immunology 2011; 22: 405–410.

Heparin Allergy: Delayed-Type Non–IgE-Mediated Allergic Hypersensitivity to Subcutaneous Heparin Injection

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and clinical symptoms of delayed-type non-IgE-mediated allergic hypersensitivity (DTH) to heparin. For diagnosis, intradermal, patch, and subcutaneous challenge tests with heparins are suitable. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Hirudin polypeptides, which exhibit a different chemical structure, are a safe therapeutic alternative for subcutaneous application, however. Importantly, despite DTH to subcutaneously injected heparins, most patients tolerate heparin intravenously. Moreover, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration without prior testing may be justified.

Diagnostics of autoimmune bullous diseases in German dermatology departments.

Background: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments.

The Complex Clinical Picture of Side Effects to Anticoagulation

Inflammatory plaques at injection sites are frequent side effects of heparin treatment and a clinical symptom of delayed-type hypersensitivity (DTH) to heparin. In most cases, changing the subcutaneous therapy from unfractionated to low-molecular-weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Because of their completely different chemical structure, hirudins are a safe alternative for anticoagulation. Despite DTH to subcutaneously injected heparins, patients tolerate heparin intravenously. Therefore, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration is justified. Skin necrosis is a rare complication of anticoagulation. Heparin-induced skin necrosis is 1 of the symptoms of immune-mediated heparin-induced thrombocytopenia and should result in the immediate cessation of heparin therapy to prevent potentially fatal thrombotic events. This is in contrast to coumarin-induced skin necrosis, where therapy may be continued or restarted at a lower dose.

c-Rel Downregulation Affects Cell Cycle Progression of Human Keratinocytes

The c-Rel protein, a member of the NF-κB transcription factor family, exerts unique and distinctive functions in various cell types. Although c-Rel is expressed in human epidermis, its functions in keratinocytes are poorly understood. Our small interfering RNA-based approach of c-Rel silencing in HaCaT keratinocytes induced altered cell morphology toward a spindle-shaped appearance. In addition, c-Rel downregulation resulted in increased apoptosis and significantly reduced proliferation towing to G2/M cell cycle delay, concomitant aberrant mitotic spindle formation, and induction of phospho-aurora A(Thr288). The relevance of c-Rel in epithelial carcinogenesis was further supported by detection of c-Rel expression in squamous cell carcinomas of the skin. Our studies indicate that c-Rel is a key regulator of cell fate decisions in keratinocytes such as cell growth and death and may have a role in epidermal carcinogenesis.

Serious complications following gluteal injection of silicone

ZusammenfassungSilikon ist ein in der Medizin vielfach eingesetztes Material und spielt unter anderem in der plastischen Rekonstruktion eine große Rolle. Die Anwendung von Silikon kann jedoch für den Patienten erhebliche, teils nicht abschätzbare Konsequenzen haben, von Schwellungen und Rötungen im Bereich der Injektionsstelle über regionale Lymphadenopathie bis hin zur Entwicklung schwerer Hautläsionen, auch fern des Applikationsortes, wie im hier geschilderten Fall einer Patientin, die wenige Jahre nach Silikoninjektion in beide Gesäßhälften massive Ulzerationen gesäßabwärts entwickelte. Darüber hinaus sind Systemreaktionen wie intrapulmonale Granulome, Embolien und assoziierte Pneumonien möglich. Auch ein Zusammenhang mit der Entwicklung von Autoimmunerkrankungen und Neoplasien wird diskutiert. Therapiemöglichkeiten bestehen in der operativen Entfernung des Materials sowie antiinflammatorischen Lokal- und Systemtherapien. Erstere ist jedoch angesichts einer diffusen Verteilung von Silikon häufig nicht vollständig möglich, für Zweitere fehlen Erfahrungswerte, vor allem im Langzeitverlauf. Flüssiges Silikon zur kosmetischen Injektion ist daher weder in Europa noch in den USA zugelassen. Aber auch bei der Verwendung von Silikonimplantaten sollte stets eine sorgfältige vorherige Abwägung und Aufklärung sowie eine Durchführung nur durch fachlich geschultes Personal erfolgen. Darüber hinaus empfehlen sich regelmäßige Nachsorgeuntersuchungen sowohl bei Implantatträgern als auch jenen Patienten, denen in der Vergangenheit flüssiges Silikon injiziert wurde.AbstractSilicone has a broad range of medical applications and plays an important role, for example, in plastic reconstruction. The use of silicone, however, may result in unpredictable consequences for the patient. These range from swelling and erythema at the site of injection and regional lymphadenopathy to the development of disseminated granulomas distant from the administration site. We report a woman who developed extensive distally-spreading ulcerations in both buttocks several years after gluteal silicone injection. Potential systemic reactions of silicone include intrapulmonary granulomas, embolism and related pneumonitis. Moreover, an association with the development of autoimmune diseases and neoplasias has been discussed. Therapeutic options include surgically removing the silicone and topical or systemic anti-inflammatory drug therapy. However, due to the diffuse dissemination of silicone, the former is often not completely possible and for the latter empirical data are limited and follow-up studies are missing. Liquid silicone is no longer authorized in Europe or in the U.S.A. When silicone implants are used, the decision should be weighed carefully and the patient adequately counseled. In addition, follow-up care on a regular basis is mandatory for both those with implants and those who obtained injections of liquid silicone in the past.Silicone has a broad range of medical applications and plays an important role, for example, in plastic reconstruction. The use of silicone, however, may result in unpredictable consequences for the patient. These range from swelling and erythema at the site of injection and regional lymphadenopathy to the development of disseminated granulomas distant from the administration site. We report a woman who developed extensive distally-spreading ulcerations in both buttocks several years after gluteal silicone injection. Potential systemic reactions of silicone include intrapulmonary granulomas, embolism and related pneumonitis. Moreover, an association with the development of autoimmune diseases and neoplasias has been discussed. Therapeutic options include surgically removing the silicone and topical or systemic anti-inflammatory drug therapy. However, due to the diffuse dissemination of silicone, the former is often not completely possible and for the latter empirical data are limited and follow-up studies are missing. Liquid silicone is no longer authorized in Europe or in the U.S.A. When silicone implants are used, the decision should be weighed carefully and the patient adequately counseled. In addition, follow-up care on a regular basis is mandatory for both those with implants and those who obtained injections of liquid silicone in the past.

The novel PI3 kinase inhibitor, BAY 80‐6946, impairs melanoma growth in vivo and in vitro

Due to its almost universal resistance to chemotherapy, metastasized melanoma remains a major challenge in clinical oncology. Given that phosphatidyl inositol‐3 kinase (PI3K) activation in melanoma cells is associated with poor prognosis, disease progression and resistance to chemotherapy, the PI3K‐Akt signalling pathway is a promising therapeutic target for melanoma treatment. We analysed six human melanoma cell lines for their constitutive activation of Akt and then tested two representative lines, A375 and LOX, for their susceptibility to PI3K‐inhibition by the highly specific small molecule inhibitor, BAY 80‐6946. In addition, the effect of BAY 80‐6946 on A375 and LOX melanoma cells was assessed in vivo in a xenotransplantation mouse model. We provide experimental evidence that specifically inhibiting the PI3K pathway and phosphorylation of Akt by this novel compound results in antitumoral activities including inhibition of proliferation, induction of apoptosis and cell cycle arrest in vitro and in vivo. However, the susceptibility did not show a clear‐cut pattern and differed between the melanoma cell lines tested, resulting in in vivo growth inhibition of A375 but not LOX melanoma cells. Thus, in some cases BAY 80‐6946 or related compounds may be a valuable addition to the therapeutic armamentarium.

Oxaliplatin-Induced Leukocytoclastic Vasculitis under Adjuvant Chemotherapy for Colorectal Cancer: Two Cases of a Rare Adverse Event

Leukocytoclastic vasculitis is a multicausal systemic inflammatory disease of the small vessels, histologically characterized by inflammation and deposition of both nuclear debris and fibrin in dermal postcapillary venules. The clinical picture typically involves palpable purpura of the lower legs and may be associated with general symptoms such as fatigue, arthralgia and fever. Involvement of the internal organs, most notably the kidneys, the central nervous system or the eyes, is possible and determines the prognosis. Oxaliplatin-induced leukocytoclastic vasculitis is a very rare event that limits treatment options in affected patients. We report 2 patients who developed the condition under chemotherapy for advanced rectal and metastatic colon carcinoma, respectively; a termination of the therapy was therefore necessary. While current therapies for colorectal cancer include the combination of multimodal treatment with new and targeted agents, rare and unusual side effects elicited by established agents also need to be taken into account for the clinical management.