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Vol. 99. Issue 6.
Pages 967-969 (1 November 2024)
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Vol. 99. Issue 6.
Pages 967-969 (1 November 2024)
Letter - Clinical
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Mimicking urticaria: a Schnitzler syndrome case
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1214
Kelielson Cardoso de Macêdo Cruza,
Corresponding author
kelielsoncma@gmail.com

Corresponding author.
, Daniela de Abreu e Silva Martineza, Danielle Carvalho Quintellab, Tullia Cuzzib, Sergio Duarte Dortas Juniora, Solange Oliveira Rodrigues Vallea
a Department of Immunology, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
b Department of Pathology, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Tables (2)
Table 1. Strasbourg diagnostic criteria of Schnitzler syndrome.
Table 2. Differential diagnoses of Schnitzler syndrome.
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Dear Editor,

Schnitzler Syndrome (SchS) is a rare disorder, with ∼350 cases reported in the literature, characterized by a neutrophilic urticarial dermatosis and monoclonal gammopathy (IgM in more than 90% of the cases), associated with clinical and biological signs of inflammation.1–3 In 2013, Lipsker, Schnitzler, and other experts met and proposed the Strasbourg diagnostic criteria, which are widely used today to diagnose SchS (Table 1).1,4 We report a case of a man with a clinical and laboratory diagnosis of SchS in Brazil.

Table 1.

Strasbourg diagnostic criteria of Schnitzler syndrome.

Obligate criteria 
- Chronic urticarial rash and 
- Monoclonal IgM or IgG 
Minor Criteria 
- Recurrent fevera 
- Objective findings of abnormal bone remodeling with or without bone painb 
- A neutrophilic dermal infiltrate on skin biopsyc 
- Leukocytosis and/or elevated CRPd 
Definite diagnosis if 
- Two obligate criteria AND at least two minor criteria if IgM and three minor criteria if IgG 
Probable diagnosis if 
- Two obligate criteria AND at least one minor criteria if IgM and two minor criteria if IgG 
a

Must be >38 °C and otherwise unexplained. Occurs usually ‒ but not obligatory ‒ together with the skin rash.

b

As assessed by bone scintigraphy, MRI, or elevation of bone alkaline phosphatase.

c

Corresponds usually to the entity described as “neutrophilic urticarial dermatosis”; absence of fibrinoid necrosis and significant dermal edema.

d

Neutrophils >10,000 mm3 and/or CRP > 3 mg/dL.

A 67-year-old man presented to our department with recurrent pruritic, not painful, urticaria-like lesions on the extremities and the trunk (Fig. 1). The lesions resolved within 24 hours without leaving behind dusky hyperpigmentation. He had intermittent fever of up to 39 °C, generalized arthralgia, and fatigue. The inflammatory episodes lasted for 2–5 days with severe general impairment. The patient suffered outbreaks with variable intensity on almost a monthly basis over the past fifteen years. Histopathology of lesional skin showed a perivascular and interstitial polymorphonuclear infiltrate, described as consistent with the diagnosis of urticarial lesions and compatible with SchS (Fig. 2).

Fig. 1.

Urticarial lesions on the trunk and left arm.

(0.09MB).
Fig. 2.

Inflammatory cells around superficial dermal vessels with neutrophils (A, Hematoxylin & eosin, ×100) also observed in the interstitial space among collagen fibers (B, Hematoxylin & eosin, ×400).

(0.79MB).

Laboratory investigations revealed leucocytosis (up to 21.000 mm3, ref 4000–11600 mm3), an elevated ESR (120 mm/hr; 0∼20 mm/hr), and increased IgM levels (2550 mg/dL; 46∼260 mg/dL) in serum protein electrophoresis (Fig. 3). In the bone scan, there is a slight asymmetry of uptake in the tibias, slightly greater on the left. Bone marrow biopsy was performed with a negative cytogenetic study for lymphoproliferative diseases. Based on these clinical and laboratory findings, he was diagnosed with Schnitzler Syndrome.

Fig. 3.

Increased IgM levels in serum protein electrophoresis test.

(0.05MB).

He was started on a high-dose corticosteroid, NSAIDs, and antihistamines with partial remission of his symptoms.

There are a few cases reported in Latin America and in general, it is underdiagnosed despite the well-established diagnostic criteria, but the pathogenesis is unknown.5

The major complication is hematological malignancy, with lymphoproliferative disorder occurring in about 10%‒20% of patients.5,6 In addition to chronic spontaneous urticaria, other differential diagnoses should be considered (Table 2).7

Table 2.

Differential diagnoses of Schnitzler syndrome.

Autoimmune diseases 
Adult Onset Still Disease (AOSD) 
Systemic Lupus erythematosus 
Acquired C1-esterase inhibitor deficiency 
Hematologic diseases 
Monoclonal gammopathy of undetermined significance (MGUS) 
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, mono-clonal gammopathy and skin changes) 
Waldenström macroglobulinemia 
Lymphomas 
Multiple myeloma 
Hereditary autoinflammatory syndromes 
Cryopyrin-associated syndromes (CAPS): 
Familial cold urticaria 
Muckle-Wells syndrome 
Chronic infantile neurologic cutaneous and articular syndrome (CINCA) 
Infectious diseases 
Hepatitis B and C 
Chronic meningococcemia 
Other 
Chronic Spontaneous Urticaria 
Hypocomplementemic urticarial vasculitis 
Delayed pressure urticaria 
Cryoglobulinemia 
Behçet syndrome 
Mastocytosis 

At present, for patients with CRP < 3 mg/dL, treatment options include, colchicine, Nonsteroidal Anti-inflammatory Drugs (NSAIDs), and hydroxychloroquine.1,2 Corticosteroids has a moderate effect and antihistamine therapy has no effect.8 According to Simon et al., the efficacy of colchicine is only 25%, but based on the benefit/risk ratio, colchicine is recommended as the first choice of treatment.9 Experts recommend the use of anakinra (IL-1 block) in more symptomatic patients, such as Erythrocyte Sedimentation Rate (ESR) and CRP above the upper limit of normal (CRP > 3 mg/dL).1

Treatment with corticosteroids, NSAIDs, and antihistamines is symptomatic and unsatisfactory.9 Anakinra (IL-1-neutralizing) is the choice drug. The effect of inhibition of IL-1 has led to new expectations, but there is currently unavailable in Brazil. An alternative drug could be canakinumab, a human anti-IL-1β monoclonal antibody aiming at the neutralization of 1β signaling.10

In patients presenting with chronic urticaria associated with signs of systemic inflammation, this rare and debilitating syndrome should be considered. Early treatment can improve patient's quality of life and disease prognosis.

Financial support

None declared.

Authors’ contributions

Kelielson Cardoso de Macêdo Cruz: Preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; approval of the final version of the manuscript; critical literature review.

Daniela de Abreu e Silva Martinez: Preparation and writing of the manuscript; approval of the final version of the manuscript.

Danielle Carvalho Quintella: Preparation and writing of the manuscript; approval of the final version of the manuscript.

Tullia Cuzzi: Preparation and writing of the manuscript; approval of the final version of the manuscript.

Sergio Duarte Dortas Junior: Preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; approval of the final version of the manuscript.

Solange Oliveira Rodrigues Valle: Preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; approval of the final version of the manuscript.

Conflicts of interest

None declared.

References
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Similarities and differences in autoinflammatory diseases with urticarial rash, cryopyrin-associated periodic syndrome and Schnitzler syndrome.
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[2]
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Chronic recurrent wheals - if not chronic spontaneous urticaria, what else?.
Allergol Select., 7 (2023), pp. 8-16
[3]
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Inflammasomes and dermatology.
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[4]
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Schnitzler syndrome: a review.
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Schnitzler’s syndrome: a case report.
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The Schnitzler syndrome: chronic urticaria and monoclonal gammopathy – an autoinflammatory syndrome?.
J Dtsch Dermatol Ges., (2008), pp. 626-631
[8]
C.Q. Chu.
Schnitzler syndrome and Schnitzler-like syndromes.
Chin Med J (Engl)., 135 (2022), pp. 1190-1202
[9]
A. Simon, B. Asli, M. Braun-Falco, H. De Koning, J.P. Fermand, C. Grattan, et al.
Schnitzler’s syndrome: diagnosis, treatment, and follow-up.
Allergy., 68 (2013), pp. 562-568
[10]
Y. Fujita, T. Asano, A. Sakai, N. Norikawa, T. Yamamoto, H. Matsumoto, et al.
A case of Schnitzler’s syndrome without monoclonal gammopathy successfully treated with canakinumab.
BMC Musculoskelet Disord., 22 (2021), pp. 257

Study conducted at the Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

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