Diagnosis

Awareness and understanding of CSU are important to ensure correct diagnosis and appropriate treatment or referral (Zuberbier et al., 2018). Guidelines for diagnosis recommend a thorough patient history and physical examination followed by routine diagnostic tests (Zuberbier et al., 20184; Powell et al., 2015). Extended diagnostic tests may be needed, based on patient history, to exclude differential diagnoses.

The 2017 International EAACI/GA2LEN/EDF/WAO guidelines recommend a three-step process for the effective diagnosis of urticaria.

The three steps recommended in the 2017 International EAACI/GA2LEN/EDF/WAO guidelines for the effective diagnosis of urticaria.

Figure 1. The three steps recommended in the 2017 International EAACI/GA2LEN/EDF/WAO guidelines for the effective diagnosis of urticaria (Zuberbier et al., 2018).
EAACI, European Academy of Allergy and Clinical Immunology; EDF, European Dermatology Forum; GA2LEN, Global Allergy and Asthma European Network; WAO, World Allergy Organization.

Patient History

Step 1

The first step in the diagnosis of urticaria should be to take a thorough patient history.

 

Recommended questions should take into consideration a number of different factors including:

  • Duration of disease
  • Physical symptoms
  • Provoking factors
  • Family history
  • Impact on everyday life
  • Previous diagnostic tests/therapy

Duration of disease

  • Time of onset
  • Frequency/duration of and provoking factors for hives
  • Diurnal variation
  • Occurrence in relation to weekends, holidays and/or foreign travel

Physical symptoms

  • Shape, size and distribution of hives
  • Associated angioedema
  • Associated symptoms (e.g. bone/joint pain, fever abdominal pain)

See also Assessment tools for disease activity and impact in CSU

Provoking factors

  • Induction by physical agents or exercise
  • Observed correlation to food

Family history

  • Family and personal history regarding wheals and angioedema
  • Previous or current allergies
  • Gastric/intestinal problems
  • Association with infections
  • Use of alternative therapeutic drugs (e.g. nonsteroidal anti-inflammatory drugs [NSAIDs], angiotensin-converting-enzyme [ACE]-inhibitors)
  • Relationship to the menstrual cycle
  • Smoking habits (especially use of perfumed tobacco products or cannabis)
  • Type of work, hobbies
  • Stress (eustress and distress)
  • Occurrence in relation to travel
     

Impact on everyday life

  • Quality of life (QoL) related to urticaria and emotional impact

See also Assessment tools for disease activity and impact in CSU

Previous diagnostic tests/therapy

  • Previous therapy and response to therapy
  • Previous diagnostic procedures/results
     
Examples of the type of questions that may be asked when taking a clinical history.

Figure 2. Examples of the type of questions that may be asked when taking a clinical history (Powell et al., 2015).

Physical Examination

Step 1

The first step in the diagnosis of urticaria should be to take a thorough patient history.

 

Physical examination should include:

  • Identification and characterisation of any current lesions
  • Diagnostic provocation tests if indicated if chronic inducible urticaria (CIndU) is suspected
  • Checking for signs of systemic illness

 

Table 1. Diagnostic provocation tests for CIndU

Diagnostic provocation tests for chronic inducible urticaria.

 

Diagnostic Tests for CSU

Step 3

As a third step, diagnostic tests should be performed as appropriate.

 

Routine Diagnostic Tests

Only very limited routine diagnostic tests should be performed in CSU and these tests should not be performed in acute urticaria.

Routine diagnostic tests in chronic spontaneous urticaria.

Figure 3. Routine diagnostic tests in CSU (Zuberbier et at., 2018).
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; NSAIDs, non-steroidal anti-inflammatory drugs.

Extended Diagnostic Tests

Extended diagnostic tests may be needed, based on patient history, to exclude differential diagnoses.

Extended diagnostic tests may be considered where directed by patient history, for identification of underlying causes and for ruling out possible differential diagnoses if indicated. Unless strongly indicated by patient history (e.g. allergy) extended diagnostic tests should not be carried out in acute spontaneous urticaria.

Extended diagnostic tests in chronic spontaneous urticaria.

Figure 4. Extended diagnostic tests in CSU (Zuberbier et at., 2018).
*Indication of severe systemic disease.

Infectious diseases

  • Bacterial, viral, parasitic or fungal infections have been implicated to be underlying causes of CSU
    • e.g., H. pylori, Streptococci, Staphylococci, Versinia, Giardia lamblia, Mycoplasma pneumonia, Hepatitis virus, Norovirus, Parvovirus B19, Anisakis simplex, Entamoeba, Blastocystis
  • The frequency and relevance of infectious diseases varies between different patient groups and geographical regions
  • More research is needed to make definitive recommendations regarding the role of infection in urticaria

Type I allergy or pseudo-allergic reactions

  • Type I allergy is a rare cause of CSU in patients who present with daily or almost daily symptoms, but may be considered in CSU patients with intermittent symptoms
  • Pseudo-allergic (non-allergic hypersensitivity) reactions to NSAIDs, food, or food additives may be more relevant for CSU with daily symptoms
  • Diagnosis should be based on an easy-to-follow diet protocol

The autologous serum skin test (ASST)

A positive ASST is indicative of CSU. The presence of autoantibodies can aid in the diagnosis of CSU. The ASST is the only test available to screen for autoantibodies in CSU, against either immunoglobulin E (IgE) or high-affinity (FcεRI) receptors. Confirmation of functional autoantibodies requires a Basophil Histamine Release Assay (BHRA) (Konstantinou et al., 2009). The ASST is the only test available to screen for autoantibodies in CSU, against either immunoglobulin E (IgE) or high-affinity (FcεRI) receptors. Confirmation of functional autoantibodies requires a Basophil Histamine Release Assay (BHRA) (Konstantinou et al., 2009).

The ASST:

  • Assesses autoreactivity in response to serum collected during active disease (Powell et al., 2015)
  • Evaluates the presence of histamine-releasing factors (including autoantibodies)
     

A positive ASST response is defined by an inflammatory red wheal response. Patients without CSU usually do not have a positive ASST response.

Lesional skin biopsy

  • If urticarial vasculitis is suspected, biopsy of lesional skin should be carried out
  • Damage of the small vessels in the papillary and reticular dermis and/or fibrinoid deposits in perivascular and interstitial locations are suggestive of UV (urticarial vasculitis)

Differential Diagnosis

While CSU is the most likely diagnosis in patients with recurrent hives and angioedema, differential diagnoses are possible.

Differential diagnoses for patients with hives and angioedema.

Figure 5. Differential diagnoses for patients with hives and angioedema (Zuberbier et at., 2018).
TNF, tumour necrosis factor; IgD, hyperimmunoglobulinemia D.

Recommended Diagnostic Algorithm for Urticaria (Zuberbier et al., 2018)

Diagnostic algorithm for chronic spontaneous urticaria.

Figure 6. Diagnostic algorithm for CSU (Zuberbier et al., 2018).