P004 Variant Schnitzler’s syndrome: a rare cause of systemic inflammation, exhaustion and intermittent urticarial rash

Background/Aims Background: Schnitzler’s syndrome is a rare autoinflammatory condition presenting with the triad of recurrent urticarial rash, monoclonal gammopathy (typically IgM), and systemic inflammation. First described in 1972, currently there are fewer than 800 cases in the literature. The clinical features of this rare syndrome overlap with many other better recognised conditions, so high clinical suspicion and awareness of this disease is essential to ensure its accurate, early diagnosis. Methods Case history: Our case is of a previously well 76-year-old Caucasian female referred to Rheumatology with an 18-month history of exhaustion, arthralgias and persistently raised inflammatory markers. Initially seen via the non-specific cancer pathway she was extensively investigated with an echocardiogram, PET scan, EBUS with lung nodule biopsy and vertebral biopsy. All results were inconclusive. Haematology MDT diagnosed MGUS due to low level IgG kappa paraprotein. During Rheumatology consultation she described intermittent, self-limiting urticarial rashes typically lasting 10 days. Often the rash coincided with “attacks of illness” every 3-4 months lasting at least 4 days, manifesting as shivers, arthralgias and exhaustion. In-between attacks fatigue was the most troublesome symptom. Examination was unremarkable. Investigations demonstrated CRP persistently >100, ESR 93, normal IgM but IgG kappa paraprotein of 3g/L. Results: Results / Management Prednisolone 30mg commenced in December 2024 resulted in rapid improvement in clinical symptoms and inflammatory markers (CRP 179 to 54 in 3-weeks), although CRP did not normalise suggesting potential ongoing subclinical inflammation. Methotrexate was commenced and steroids weaned by May 2025. Interestingly, within a few weeks the rash, arthralgia and fatigue returned, rendering the patient almost housebound. CRP rose to 248. Steroids were re-commenced and symptoms settled within 48 hours. Given the presentation of a steroid-responsive inflammatory syndrome, with episodic urticarial rash and IgG kappa paraprotein, a diagnosis of variant Schnitzler’s syndrome was made. Gold standard treatment of Schnitzler’s syndrome is with daily anakinra and typically a rapid response can be expected within days. Treatment response is also an important part of the diagnostic work-up and can help confirm correct diagnosis. Following initiation of anakinra in June 2025, this patient’s symptoms significantly improved and her inflammatory markers normalised. Conclusion Our case highlights the importance of considering Schnitzler’s syndrome as a possible diagnosis in patients with urticarial rash and systemic inflammation, even without classical IgM monoclonal gammopathy. Clinician awareness of this rare condition is crucial to ensure correct clinical diagnosis, which can then be supported by Lipsker or Strasbourg diagnostic criteria. Timely and correct diagnosis also enables prompt treatment with anakinra, which should result in a dramatic resolution of symptoms, normalisation of inflammatory markers and prevention of long-term complications. Treatment response is also an important part of the diagnostic work-up and can help confirm correct diagnosis.