Corneal melt secondary to eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis that can affect any organ system. It is most often characterised by chronic airway inflammation along with prominent peripheral blood eosinophilia, although the disease can affect the cardiovascular, gastrointestinal, renal or central nervous systems. Ocular manifestations are uncommon and when they do occur, are varied in their clinical presentations. To the best of our knowledge, this is the first case of corneal melt secondary to EGPA to have been reported.

Diagnostics and therapy of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides.

Granulumatosis with polyangiitis (wegener's)/GPA microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS) are primary systemic vasculitides which predominantly affect small vessels, showing a high association with a positive C/PR3-ANCA in GPA and P/MPO-ANCA in MPA, so called ANCA-associated vasculitides (AAV). The diagnostic work-up relies on an interdisciplinary approach including imaging techniques and laboratory tests in order to assess disease stage and extent. The golden standard remains the histological proof of a necrotizing, pauci-immune small vessel vasculitis, in GPA additionally non-caseating granuloma is found mainly in the respiratory tract. Treatment is adapted to disease stage and extent and relies on a combination of a cytotoxic plus a tapering regimen of glucocorticosteroids. Induction of remission in "early systemic" disease without organ- and life-threatening organ manifestations and a near normal kidney function can be achieved with methotrexate. In the generalized phase with significant renal dysfunction cyclophosphamide is the mainstay of therapy, in rapidly progressive glomerulonephritis with an imminent dialysis indication plasmapheresis is performed additionally. When remission is achieved, usually after 3-6 months of induction treatment, cyclophosphamide is switched to azathioprine as maintenance of remission drug. Alternative therapies are methotrexate provided the kidney function is normal or Leflunomide in the long-term follow-up the relapse rate in ANCA-associated vasculitis is approximately 50% in 5 years, irrespective of the drug used for maintenance treatment. The relapse rate is significantly higher in GPA than in MPA and CSS.

Wegener's Granulomatosis vasculitis and granuloma.

Wegener's Granulomatosis (WG) is an autoimmune disease with manifestations in different organ systems. The hallmark of WG is a necrotizing granulomatous inflammation of the upper and/or lower respiratory tract and systemic small vessel vasculitis which can involve multiple organ systems. The treatment of WG has evolved over the last decades. Steroid, cytotoxic and biologic therapies have been used leading to great improvements in outcome. However, still mortality is high and relapses are a major cause of mortality and morbidity. Despite intensified maintenance regimens and new possibilities of biologic therapies in WG the relapse rate is high. Even patients treated with high dose cytotoxic therapies in autologous stem cell treatment protocols have shown relapses in the course of disease. Increasing knowledge of the pathophysiology of granuloma in WG and new biologic therapies might be of great importance for future treatment of WG.

Biological therapies: new treatment options for ANCA-associated vasculitis?

Biological therapies enable us to apply highly selective targeting components to modulate the immune response. Until now, a few controlled studies investigated the efficacy of TNF-alpha blocking agents in systemic vasculitis have been carried out, but, in general, they were falling short of expectations. However, there is conducive evidence that TNF-alpha blockers are advantageous in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, at least in selected disease stages. Likewise, although the efficacy of the monoclonal CD20 antibody rituximab in ANCA-associated vasculitis is obvious, the effect on predominantly granulomatous disease activity in Wegener's granulomatosis is less clear. In addition, interferon-alpha is used for induction treatment particularly in Churg-Strauss syndrome. Even though the effectiveness and safety of short-term administration was confirmed by case series, severe side effects after long-term treatment relativized the initial results. This review presents the recent data on the use of biologicals in vasculitis and appraises the knowledge in the clinical context.

Wegener granulomatosis in children and adolescents: clinical presentation and outcome.

We prospectively studied and compared clinical features, treatment, course of illness, and long-term morbidity and mortality rates for Wegener granulomatosis in 23 childhood-onset patients with those of 135 adult-onset patients who were studied concurrently. Treatment was usually provided with glucocorticoids and cyclophosphamide. The mean follow-up period was 8.7 years for childhood-onset and 7.6 years for adult-onset Wegener granulomatosis. Most aspects of Wegener granulomatosis were similar in childhood-onset and adult-onset patients. Permanent morbidity from disease occurred in 86% of both groups. However, some features were significantly different. Wegener granulomatosis in childhood-onset patients was complicated five times more often by subglottic stenosis and twice as often by nasal deformity. Treatment-related permanent morbidity occurred in 22% of childhood-onset patients and 45% of adult-onset patients. After similar periods of cyclophosphamide therapy and follow-up, cyclophosphamide-related malignancies were less likely (0% vs 11%) to have developed in childhood-onset patients. Although 89% of patients treated with glucocorticoids and cyclophosphamide had remission, prolonged delay in achieving remission and relapses led in both patient groups to freedom from active disease for approximately 50% of the total patient-years. As a result, morbidity was substantial and has led to comparative studies of alternative therapies.

[Facial and head pain from the neurologist's point of view (author's transl)]. / Der Gesichts- und Kopfschmerz aus der Sicht des Neurologen

Recognizing that pain is not a sensory sensation, but a subjective feeling, the neuroanatomical and neurophysiological aspects are shortly discussed which are the prerequisites of pain as an original phenomenon in higher life. The subcortical feeling of pain is compared with the pain sensation which extends to large parts of the cortex. The experience of pain may be suppressed or increased by the cortex. Since pain as a subjective phenomenon cannot be objectivated directly, the pain analysis has to consider the history of the patient and particularly the anatomical and physiological basis. The clinical diagnosis of facial and head pain differentiates the various pain syndrome which as localized pain are usually caused by externally visible changes from those projected pain phenomena in genuine or symptomatic neuralgias as well as referred pain sensations (e.g. in intracranial or occipitocervical lesions).