Schnitzler Syndrome With Delirium and Vertigo: The Utility of Neurologic Manifestations in Diagnosis
June 2017 | Volume 16 | Issue 6 | Case Reports | 625 | Copyright © June 2017
Stanislav N. Tolkachjov MDa and David A. Wetter MDb
aSurgical Dermatology Group, Birmingham, AL bDepartment of Dermatology, Mayo Clinic, Rochester, MN
Schnitzler syndrome (SS) is an autoinflammatory dermatosis that often goes undiagnosed for 5-6 years. Patients typically carry a diagnosis of urticaria; however, their cutaneous symptoms fail to respond to typical urticaria therapies and lack symptoms such as pruritus. Additionally, patients with SS may see multiple providers for nonspecific complaints of fever, lymphadenopathy, arthralgias, and bone pain. A correct diagnosis is paramount, as close to 20% of patients may develop a lymphoproliferative disorder and appropriate treatment may ameliorate all symptoms.1
We report 2 cases of SS misdiagnosed as urticaria for years in order to illuminate diagnostic pearls, histopathological findings, and treatment modalities. Additionally, we highlight the importance of neurologic disturbances in this rare but important differential diagnosis of urticaria.
J Drugs Dermatol. 2017;16(6):625-627.
Case 1: An 80-year-old male presented with 8 months of recurrent fevers, rashes, lymphadenopathy, arthralgias, confusion, and delirium that coincided with the febrile episodes. On clinical exam, 50% of his trunk demonstrated confluent urticarial plaques that resolved over 1 to 2 days (Figure 1a and b). On laboratory evaluation, he had immunoglobulin-M (IgM) kappa monoclonal gammopathy and an elevated erythrocyte sedimentation rate (ESR).Case 2: A 56-year-old female was referred for 31 months of recurrent non-pruritic urticaria, elevated ESR/CRP, febrile sensation, and recurrent vertigo. She failed high-dose antihistamines and omalizumab. On exam, urticarial plaques were noted on her trunk and extremities (Figure 1c). Laboratory evaluations included an elevated ESR, C-reactive protein (CRP), IgM kappa monoclonal gammopathy, and an elevated white cell count with neurophilic shift.Histopathology in both patients demonstrated neutrophilic dermal interstitial and perivascular inflammation consistent with a neutrophilic urticarial dermatosis (Figure 2).Prior to presentation, both patients had neurologic evaluations for delirium and vertigo, respectively.
Schnitzler syndrome (SS) is characterized by a recurrent urticarial rash, accompanied by intermittent fever, arthralgia or arthritis, and bone pain. Monoclonal gammopathy, lymphadenopathy, leukocytosis, and elevated serum inflammatory markers are also seen.2 Patient 1 demonstrated both of the major diagnostic criteria, urticarial rash and an IgM kappa monoclonal gammopathy; and minor criteria of intermittent fevers, arthralgias, lymphadenopathy, and elevated ESR.Patient 2 met both major criteria and minor criteria of leukocytosis, fever, as well as elevated ESR/CRP.Along with fever and potential lymphadenopathy, clinical keys in patients with chronic urticaria that raise suspicion for SS are the non-pruritic nature of the urticaria, lack of bruising with resolving plaques, sparing of the face, and failure to respond to antihistamines.3 Patients with SS may also demonstrate characteristic findings of osteosclerosis on a bone scan, specifically in the areas of the knees and pelvis. Radiologic imaging may be ordered to help with the diagnosis; however, a radiologist should be alerted about the reason for the evaluation.4 In our cases, the strong association of neurologic symptoms of confusion/delirium and vertigo were helpful in alerting the clinician to order monoclonal protein studies to evaluate for an IgM gammopathy.Patients with idiopathic chronic urticaria typically have intense pruritus, an increased chance of responding to antihistamines, and lack fever. Additionally, the lack of bruising on resolution clinically differentiates urticaria from urticarial vasculitis. While only rarely reported, the neurologic findings, as described in this series, are helpful in evaluating for a systemic inflammatory etiology of recurrent urticaria.2;5-8 Histopathology in most cases demonstrates perivascular and interstitial neutrophilic