Vnitr Lek 2008, 54(12):1140-1153

Schnitzler syndrome - report on a fourteen-year course of the disease and an overview of information on the disease

Z. Adam^1,*, M. Krejčí¹, L. Pour¹, J. Neubauer², J. Prášek³, R. Hájek¹

¹ Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc.

² Radiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Vlastimil A. Válek, CSc., MBA

³ Klinika nukleární medicíny Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta doc. MUDr. Jiří Prášek, CSc.

Schnitzler syndrome is a rare disease characterised by chronic urticaria and the presence of monoclonal IgM immunoglobulin, and by other symptoms. We report our experience with 14-year treatment of a patient. The first medical examination in our workplace was at the beginning of 1995 and the patient was diagnosed with the disease in 1996 (at the age of 52). Antihistaminics, the first medication used to relieve the symptoms of urticaria, had no subjective or objective effect. After the detection of osteolytic-osteosclerotic changes in the pelvic region, in areas with intense pain, we started treatment with pamidronate (90 mg at 28-day intervals), and the pain disappeared completely within 3 months of application of the drug. When the bisphosphonate therapy was interrupted, the pain recurred and receded completely after renewal of bisphosphonate administration. After the diagnosis, we gave the patient high doses of dexametazone (40 mg day 1-4, 10-13 and 20-23, at 28-day cycles). However, the therapy suppressed urticaria only on the days dexametasone was administered and the effect did not last when the drug was discontinued. Therefore we moved to continuous daily doses of prednisone (10-30 mg, depending on the intensity of problems), which was the only therapy with a long-term effect which was relatively well tolerated at the same time. Based on the excellent effect of 2-chlordeoxyadenosine in Waldenström's macroglobulinaemia, three cycles of this therapy were administered to the patient in 1996 (0.1 mg/kg/day, 7 days, at 28-day intervals). After the first infusion, urticarious lesions disappeared, but the positive effect on skin eruptions was limited in time and lasted only 14 days after the last infusion, i.e. the medication proved ineffective from a long-term point of view. The first improvement lasting for a longer period of time (partial remission) was achieved by regular application of interferon α (3 QU 3 times a week). However, adverse effects of interferon α prevailed after two years and the therapy was discontinued. Similarly phototherapy using the PUVA method resulted in partial regression of urticarious symptoms. Subsequently tested cyclosporine A (5 mg/kg/day) brought no benefit. Thalidomide (100 mg in the evening) administered on a continuous basis relieved pruritus and improved sleep disturbed by pruritus. However, adverse effects prevailed after 4 months and the therapy had to be discontinued, too. In 2005, we were hoping to achieve positive results with the most effective treatment for multiple myeloma of the time, a combination of bortezomib (1.3 mg/m² i.v. on day 1, 4, 8 and 11, thalidomide 100 mg daily and dexametazon 20 mg p.o. on days 1-4 and 8-11 in 21-day cycles - VTD). A total of 4 complete cycles and 4 cycles with bortezomib reduced by 50% were applied. Urticarious eruptions were reduced by at least 50% in the course of the therapy, and also the concentration of monoclonal immunoglobin decreased temporarily by more than 50%. However, after the therapy was discontinued, the symptoms returned with their original intensity, which means that VTD regime did not provide a long-term therapeutic response. In 2007, we started the anakinra (Kineret) therapy. Skin symptoms disappeared after the first injection and a dose of 100 mg/day has kept the patient free of skin symptoms for 12 months by now. Also the CRP value which had been constantly high returned to normal, and haemoglobin values increased to achieve physiological range. In the course of 14 years, we confirmed partial therapeutic effect of glucocorticoids administered on a continuous basis, as well as a partial therapeutic effect of interferon α, thalidomide and PUVA, but all the therapies had to be discontinued due to adverse effects. A major turn, i.e. the complete disappearance of skin symptoms and normalisation of CRP and haemoglobin values, only came with anakinra which has become the drug of the first choice for the above syndrome.

Keywords: anakinra; bortezomib; bisphosphonates; cyclosporine A; interferon α; thalidomide; 2-chlordeoxyadenosin; Schnitzler syndrome; monoclonal gammopathy; Waldenström's macroglobulinaemia; multiple myeloma

Received: May 12, 2008; Accepted: July 22, 2008; Published: December 1, 2008  Show citation