Chronic recurrent wheals – If not chronic spontaneous urticaria, what else?

Abstract

Chronic urticarial rash, mostly due to chronic spontaneous urticaria (CSU), is seen in up to 1 – 4% of the general population. Urticarial vasculitis (UV) and autoinflammatory syndromes, i.e., cryopyrin-associated periodic syndromes (CAPS) and Schnitzler syndrome (SchS), can mimic CSU-like rash but represent rare disorders with systemic symptoms including fever, headache, conjunctivitis, and arthralgia. Clinical and laboratory features can point to the presence of any of these diseases in patients initially presenting with chronic urticarial rash. These include long-lasting wheals (> 24 hours), lesional burning, systemic symptoms, and/or increase in inflammatory markers (e.g., C-reactive protein, serum amyloid A, and/or S100A8/9). Lesional skin biopsy usually demonstrates leukocytoclastic vasculitis (UV) or neutrophil-rich infiltrate (CAPS and SchS). In contrast to CSU, where second-generation H1 antihistamines and omalizumab allow to control symptoms in most patients, systemic immunosuppression and anti-interleukin (IL)-1 therapies are needed in case of UV and autoinflammatory diseases, respectively. The rarity and low awareness of CSU differential diagnoses may be related to the longer delays in diagnosis and therapy in those affected with UV, CAPS, and SchS. Knowledge of the differential diagnoses of CSU is important because only correct diagnosis allows adequate therapy. Complications such as the development of lymphoproliferative disease in SchS and amyloidosis in CAPS, and the presence of comorbid diseases, such as systemic lupus erythematosus in UV, must be considered and monitored.

A Practical Approach to Diagnosing and Managing Chronic Spontaneous Urticaria

“…A checklist of items to consider during history taking is included in Table 1 [ 50 ]. It is important to obtain sufficient detail from the patient to streamline the diagnostic process and prevent the need for multiple consultations [ 50 , 51 ]. Important questions to ask patients with suspected CSU, that will help rule out other diagnoses, are included in Table 2 .…”

The many faces of pediatric urticaria

“…When the clinical presentation shows the early onset of recurrent urticaria without itching, triggered by cold, fever, constant musculoskeletal pain, fatigue, and listlessness, CAPS should be considered in the differential diagnosis (88). The diagnosis of CAPS is based on clinical presentation, family history, and genetic testing to identify mutations in the NLRP3 gene, although confirmed NLRP3 gene mutation can be demonstrated only in 40% of individuals affected by CAPS (88). A dramatic response to IL-1β neutralizing drugs is usually observed in treatment.…”

Prevalence of Autoimmune and Autoinflammatory Diseases in Chronic Urticaria: Pathogenetic, Diagnostic and Therapeutic Implications

“…Autoinflammatory diseases (Cryopyrin-Associated Periodic Syndrome (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome (SchS), Adult Still's Disease (AOSD)) represent a group of chronic disabling diseases characterized by a condition of direct selfinflammation, mediated by disturbances in innate immune signalling pathways [80]. Specifically, an excessive secretion of cytokines by innate immune cells (such as macrophages, monocytes) is observed, among which we mention the group of interleukin (IL)-1, which, accumulating at the level of different tissues and systems, lead to the clinical development of disease.…”