Schnitzler syndrome is a
rare disease characterised by
chronic urticaria and the presence of monoclonal
IgM immunoglobulin, and by other symptoms. We report ourexperience 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 alpha (3 QU 3 times a week). However, adverse effects of
interferon alpha 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 alpha,
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.