Classification of urticaria.

Classification is based on GA(2)LEN/EAACI/WAO/EDF guidelines (2009). These guidelines classify urticaria according to clinical manifestations. Urticaria is mediated by mast cells. According to level of mast cell degranulation clinical signs are superficial (Urticaria) or deep swelling (Angioedema).

Introduction

This chapter is based on the latest GA2LEN/EAACI/WAO/EDF guidelines (2009), which classify urticaria based on clinical symptoms, duration, and frequency. Because of the overlap between the underlying mechanisms of the different subtypes of urticaria, a classification based on the underlying mechanisms – which was attempted earlier – is less useful.

Urticaria has been described as a medical entity since antiquity. However, only in the last century was there a better understanding of the different subtypes showing the high heterogeneity the disease. Misnomers such as urticaria pigmentosa, which in fact is a cutaneous manifestation of mastocytosis, were revealed. Similar to urticarial vasculitis, these diseases due to historical reasons are still often addressed in urticaria book chapters, but in this case the wheal-like symptoms are not true wheals since they last longer and are not histamine-mediated but based on the true vasculitis occurring in superficial cutaneous vessels.

Furthermore, it needs to be noted that the symptom of urticaria – the wheal – can also occur under other circumstances as a kind of bystander effect, such as in acute anaphylaxis or in association with syndromes such as Muckle-Wells syndrome.

Thus, in conclusion, an important aspect in the guideline work was first of all to have clear-cut definitions of the disease and its symptoms, always remembering that overlap is possible in the classical medical nomenclature. This also holds true for the term angioedema, which can be histamine-induced, associated with urticaria, or even the sole manifestation of urticaria, but can also occur due to bradykinin formation, for example, in hereditary angioedema or in other, unrelated dermatological diseases, as a symptom, such as in cheilitis granulomatosa.

Urticaria is a disease characterized by the appearance of wheals and/or angioedema, encompassing several subtypes. Diagnosis and treatment vary according to the subtype, so classification is important. The symptoms of urticaria (wheals and/or angioedema) can also occur in other conditions or diseases, for example, anaphylaxis.

Wheals are itchy or burning swellings, variable in size, often surrounded by reflex erythema, and of a fleeting nature, lasting anywhere from 1-24 h before disappearing.

Angioedema is defined as sudden, pronounced swelling of the lower dermis and sub-cutis, sometimes painful rather than itchy, and taking up to 72 h to resolve. Angioedema frequently involves the mucous membranes.[1]

Classification of Urticaria

Old systems of classification in urticaria were often driven by pathophysiology, for example, classifying urticaria in allergic urticaria, urticaria due to infectious agents, or autoimmune urticaria. With a better understanding of the pathophysiology, this is no longer useful, since there is a high overlap between the different forms in the underlying pathophysiology. For example, allergic urticaria can occur in acute and chronic urticaria forms, and contact urticaria, just to name some, and the same holds true for the term “automimmune urticaria,” which was originally devised when high-affinity IgE-receptor antibodies were discovered in chronic urticaria (Hide et al.).[2] With progress and knowledge it now becomes apparent that also other subtypes, for example, in cholinergic urticaria, autoimmune phenomena appear to be playing a role. Based on these considerations, the current guidelines classified urticaria based on the clinical manifestation, which makes it much easier for the practicing doctor to better diagnose the patients. In this classification, of course, there are also sometimes points that need to be discussed for better understanding. Thus the term chronic urticaria is strictly reserved for spontaneous appearance of wheals (to better show this, the term chronic spontaneous urticaria was introduced), but this does not mean that the physical subtypes of urticaria are not chronic; in these cases, symptoms are not chronic but only visible when physical stimuli are present.[3]

Table 1 summarizes the classification. Note that the clinical manifestations of urticaria are broad and patients may exhibit two or more subtypes at one time.

Table 1

Urticaria subtypes-classification

Some conditions formerly classified as urticaria are no longer considered to be subtypes of urticaria. These include urticaria pigmentosa (cutaneous mastocytosis), urticarial vasculitis, familial cold urticaria, and non-histaminergic angioedema (hereditary or acquired angioedema). Some subtypes of urticaria appear in conjunction with other syndromes such as Muckle-Wells [Table 2].

Table 2

Diseases related to urticaria for historical reasons and syndromes, including urticaria and/or angioedema

In order to properly classify urticaria, the following factors must be taken into consideration (see Figure 1 for a flow chart on differential diagnosis):

Figure 1

Differential diagnosis.[4] (Modified from: Zuberbier T, Bindslev - Jensen C, Canonica W, Grattan CE, Greaves MW, Henz BM, et al. EAACI/GA2LEN/ EDF guideline: Definition, classification and diagnosis of urticaria. Allergy 2006;61:316-20.)

Are there physical triggers or other external factors? If so, measure the intensity of the eliciting factor, for example, how long does pressure need to be applied, and how much, in pressure urticaria; or temperature and time of exposure in cold urticaria.

For non-physical urticarias, guidelines suggest a unified scoring system from 0 (no wheals) to 3 (intense, many wheals, longer than 24 h).

Ask patients to record their symptoms and self-evaluate according to the scoring system. Self-evaluation is important since intensity fluctuates over the course of 24 h. Self-evaluation can be supported by a periodic or one-time medical examination to ensure objectivity in the self-scoring.

General Issues

Wheal size sometimes indicates the severity of the disease: larger wheals means the urticaria is more severe and harder to treat. Wheal color may also help in diagnosis, as lighter colored wheals with a pink erythema indicate the involvement of histamine; pink erythema is the result of dilatation of cutaneous vessels. Dark red or violaceous wheals are associated with vascular damage and leakage, perhaps indicating urticaria vasculitis.

Last but not the least, it is also important to monitor disease intensity and appearance of wheals during the course of treatment. Very often, pre- and post-treatment comparison may also reveal the factors indicating the underlying course. Ideally, this evaluation should be accompanied by evaluation of the quality of life for which specialized instruments have been devised for urticaria (Baiardini).[1]