Schnitzler's Syndrome: A Case Report

Schnitzler's syndrome is an extremely rare entity that poses a challenge for the clinician not only due to its difficult diagnosis but also due to its management. In this article we report a new case and briefly review the current treatment options.

To date only around 100 cases [1,2,8] have been reported since the first described case in 1972 [9].
This autoinflammatory syndrome clinically presents with a diverse constellation of symptoms making its initial diagnosis very challenging. Its early recognition is key due to the increased risk of lymphoproliferative disorders (10-15% per year [2]) and its tremendous impact on the quality of life of the patients with this entity.

Case Report
A 49-year-old Caucasian female presented with generalized arthralgias and recurrent diffuse pruritic maculopapular lesions over her face, torso, and upper extremities. The patient suffered outbreaks with variable intensity almost in a daily basis over the past five years with no identifiable triggering factors.
The patient mentioned that the lesions cleared up in 24 hours, leaving no marks or scars, while new lesions appeared daily.
Her past medical history was significant for transfusion related hepatitis C, diabetes mellitus type 2, depression, chronic pancreatitis, and malnutrition.
She had a 35 pack/year history of smoking, with remote history of inhaled crack cocaine use. She denied alcohol or other illicit drug use.
Review of systems revealed unintended weight loss of about 20 pounds over a 6-month period, diffuse abdominal pain, generalized weakness, night sweats, and subjective recurrent low-grade fevers not associated with the onset of her skin lesions.  Her family history was noncontributory (father deceased at the age of 70 because of heart disease, mother had diabetes mellitus and coronary artery disease, and her brother and daughter had good health).
The initial physical examination revealed diffuse pruritic maculopapular lesions over her face, thorax, and upper extremities (Figure 1), sparing her palms, soles, and mucous membranes. Also mild hepatosplenomegaly was found.
Her laboratory studies showed marked leukocytosis of 48.6 with neutrophils of 97.8% with elevated D-dimer and erythrocyte sedimentation rate (ESR) ( Table 1).
She was started on broad-spectrum antibiotics that were discontinued 72 hours after the admission when infections were ruled out.
Based on the clinical presentation and laboratory results the diagnosis of Schnitzler syndrome was made. As proposed by Lipsker et al. [3] the diagnosis of this entity requires 2 major criteria and a minimum of 2 minor criteria. She had 2 major criteria (chronic urticarial rash/intermittent fever and monoclonal IgM) plus at least 5 minor criteria (arthralgias, bone pain, lymphoadenopathy, hepato-and/or splenomegaly, and elevated ESR and/or leukocytosis).
She was started on high dose of corticosteroids, nonsteroidal anti-inflammatory drugs, and antihistamines with partial remission of her symptoms and she was discharged home (Figure 2).
Anakinra was added to her regimen for several weeks with an excellent response; however due to economical constrains treatment was discontinued, and her symptoms partially recurred.

Conclusions
Schnitzler's syndrome is an underdiagnosed disease with only around 100 cases reported in the literature. Having eastern European origin [1,2,7,8] and being a woman (women are more frequently affected than man (1.6 : 1) [2]) are strong associations to this entity.
The mortality risk is not increased in patients with Schnitzler's syndrome (survival of 94% after 15 years of the diagnosis) [2]; however there is a well-established increased risk of malignancy (specially lymphoproliferative disease such as Waldenström macroglobulinemia and IgM myeloma) of 10-year risk of 15% [2,31]. Systemic steroids remain as the first line of treatment [3,8,10], being effective to less than a half of the patients [8]. The data available demonstrated that the treatment of Schnitzler syndrome is not standardized, and there are promising results with new biological therapies such as the interleukin-1 receptor antagonist Anakinra [12,[20][21][22][23][24], Rituximab [25,26], and Tocilizumab [27,28].

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Conflict of Interests
The authors declare that they have no conflict of interests.

Authors' Contribution
Gabriel Tinoco, Rehan Kanji, and Deepthi Moola reviewed and analyzed the patient data and wrote the paper. All authors read and approved the final paper.